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What is epigenetics

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Centers for Disease Control and Prevention

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Your genes play an important role in your health, but so do your behaviors and environment, such as what you eat and how physically active you are. Epigenetics is the study of how your behaviors and environment can cause changes that affect the way your genes work. Unlike genetic changes, epigenetic changes are reversible and do not change your DNA sequence, but they can change how your body reads a DNA sequence.

Gene expression refers to how often or when proteins are created from the instructions within your genes. While genetic changes can alter which protein is made, epigenetic changes affect gene expression to turn genes "on" and "off." Since your environment and behaviors, such as diet and exercise, can result in epigenetic changes, it is easy to see the connection between your genes and your behaviors and environment.

How Does Epigenetics Work?

Epigenetic changes affect gene expression in different ways. Types of epigenetic changes include:

DNA Methylation

DNA methylation works by adding a chemical group to DNA. Typically, this group is added to specific places on the DNA, where it blocks the proteins that attach to DNA to "read" the gene. This chemical group can be removed through a process called demethylation. Typically, methylation turns genes "off" and demethylation turns genes "on."

Histone modification

DNA wraps around proteins called histones. DNA wrapped tightly around histones cannot be accessed by proteins that "read" the gene. Some genes are wrapped around histones and are turned "off" while some genes are not wrapped around histones and are turned "on." Chemical groups can be added or removed from histones and change whether a gene is unwrapped or wrapped ("on" or "off").

Non-coding RNA

Your DNA is used as instructions for making coding and non-coding RNA. Coding RNA is used to make proteins. Non-coding RNA helps control gene expression by attaching to coding RNA, along with certain proteins, to break down the coding RNA so that it cannot be used to make proteins. Non-coding RNA may also recruit proteins to modify histones to turn genes "on" or "off."

How Can Your Epigenetics Change?

Your epigenetics change as you age, both as part of normal development and aging and in response to your behaviors and environment.

Example: Nerve cell vs. Muscle cell

Your muscle cells and nerve cells have the same DNA but work differently. A nerve cell transports information to other cells in your body. A muscle cell has a structure that aids in your body's ability to move. Epigenetics allows the muscle cell to turn "on" genes to make proteins important for its job and turn "off" genes important for a nerve cell's job.

Example: Study of newborn vs. 26-year-old vs. 103-year-old

DNA methylation at millions of sites were measured in a newborn, 26-year-old, and 103-year-old. The level of DNA methylation decreases with age. A newborn had the highest DNA methylation, the 103-year-old had the lowest DNA methylation, and the 26-year-old had a DNA methylation level between the newborn and 103-year-old ( 1).

Example: Smokers vs. non-smokers vs. former smokers

Smoking can result in epigenetic changes. For example, at certain parts of the AHRR gene, smokers tend to have less DNA methylation than non-smokers. The difference is greater for heavy smokers and long-term smokers. After quitting smoking, former smokers can begin to have increased DNA methylation at this gene. Eventually, they can reach levels similar to those of non-smokers. In some cases, this can happen in under a year, but the length of time depends on how long and how much someone smoked before quitting ( 2).

Epigenetics and Health

Epigenetic changes can affect your health in different ways:

Example: Mycobacterium tuberculosis

Mycobacterium tuberculosis causes tuberculosis. Infections with these germs can cause changes to histones in some of your immune cells that result in turning "off" the IL-12B gene. Turning "off" the IL-12B gene weakens your immune system and improves the survival of Mycobacterium tuberculosis ( 3).

Cancer
Certain mutations make you more likely to develop cancer. Likewise, some epigenetic changes increase your cancer risk. For example, having a mutation in the BRCA1 gene that prevents it from working properly makes you more likely to get breast and other cancers. Similarly, increased DNA methylation that results in decreased BRCA1 gene expression raises your risk for breast and other cancers (4).While cancer cells have increased DNA methylation at certain genes, overall DNA methylation levels are lower in cancer cells compared with normal cells. Different types of cancer that look alike can have different DNA methylation patterns. Epigenetics can be used to help determine which type of cancer a person has or can help to find hard to detect cancers earlier. Epigenetics alone cannot diagnose cancer, and cancers would need to be confirmed with further screening tests.

Example: Colorectal Cancer

Colorectal cancers have increased methylation at the SEPT9 gene. Some commercial epigenetic-based tests for colorectal cancer look at DNA methylation levels at the SEPT9 gene. When used with other diagnostic screening tests, these epigenetic based tests can help find cancer early ( 5)( 6).

Nutrition During PregnancyA pregnant woman's environment and behavior during pregnancy, such as whether she eats healthy food, can change the baby's epigenetics. Some of these changes can remain for decades and might make the child more likely to get certain diseases.

Example: Dutch Hunger Winter Famine (1944-1945)

People whose mothers were pregnant with them during the famine were more likely to develop certain diseases such as heart disease, schizophrenia, and type 2 diabetes ( 7). Around 60 years after the famine, researchers looked at methylation levels in people whose mothers were pregnant with them during the famine. These people had increased methylation at some genes and decreased methylation at other genes compared with their siblings who were not exposed to famine before their birth ( 8)( 9)( 10). These differences in methylation could help explain why these people had an increased likelihood for certain diseases later in life ( 7)( 10)( 11)( 12).

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office of genomics and precision public health

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Your genes play an important role in your health, but so do your behaviors and environment, such as what you eat and how physically active you are. Epigenetics is the study of how your behaviors and environment can cause changes that affect the way your genes work.

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Can Your Environment Affect Your DNA? | Epigenetics Explained

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The expression “nature vs. nurture” describes the question of how much a person’s characteristics are formed by either “nature” or “nurture.” “Nature” means innate biological factors (namely genetics), while “nurture” can refer to upbringing or life experience more generally.

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Nature vs nurture - Gina

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Nature vs. Nurture: What Science Really Knows

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Nature, nurture, or both? Vic Katch discusses the relationship between genetics and lifestyle choices for enhancing health.

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National Institute of Medicine

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Abstract

The contentious nature-nurture debate in developmental psychology is poised to reach a rapprochement with contemporary concepts of gene-environment interaction, transaction, and fit. Discoveries over the past decade have revealed how neither genes nor the environment offers a sufficient window into human development. Rather, the most important discoveries have come from unearthing the manner in which the environment alters gene expression (and how genes impose limits on environmental effects), how biology and the environment influence each other across time, and how maximizing gene-environment fit leads to optimal outcomes for children. The manner in which these factors operate in tandem should direct future scholarship, practice, and public policy.

Perhaps the most important, and certainly the most contentious, debate in the history of developmental psychology has concerned the fundamental question of the role of genetic and biological factors versus environmental and learning factors in a child's development. This debate is rooted in philosophical arguments about the nature of the human species as a tabula rasa ( Locke, 1690/1913) to be shaped by experience versus a "noble savage" to be reined in by environmental constraints on a biological destiny ( Hobbes, 1651/1969). Much of the modern study of individual differences in behavioral development through longitudinal inquiry in the 1950s and 1960s inexplicably ignored the role of innate factors but led to unprecedented publicly funded programs (e.g., Head Start) to enrich the early environments of economically disadvantaged children in a War on Poverty ( Zigler & Muenchow, 1992). This work had dual premises that disparities across groups were largely a result of environmental disadvantage and that environmental enrichments could repair this inequity.

The naive hope that early environments could be easily manipulated to alter long-term outcomes inspired a backlash of behavior-genetic studies in the 1980s and 1990s that championed the high percent of variance in behavior that is accounted for by genes. The legacy of this backlash is the argument that public and private resources (e.g., the best schools and highest incomes) should be administered according to selection of those with the highest (presumably, genetically based) potential to achieve, rather than to compensate for biological or environmental disadvantage ( Herrnstein & Murray, 1994). The scholarly anchor for the policy conclusion was exemplified in essays by Scarr (1992), Lytton (1990), and Harris (1995, 1998) which claimed that the environment accounts for very little influence on human behavior. After 50 years of study, it seemed that little had been learned.

Fortunately, the turn of the 21st century has brought ground-breaking findings that should bring this debate to a rapprochement and new level of sophistication. As highlighted by the National Academy Panel on early childhood development ( National Research Council, 2000), these findings suggest a remarkably intimate relation between genes and the environment that is played out in interaction effects, transaction effects, mediational effects, and even evolutionary effects. This commentary will review this progress, forecast the next decades of inquiry, and suggest that these new concepts should direct public policy toward children.

Apportioning the Variance in Human Behavior

One of the problems with the gene-environment debate has been that scholars have employed different ways of aggregating measures of behavior in order to estimate gene and environment effects. By doing so, they have asked different questions, but the debate has failed to capture these nuances. Consider Scarr's (1992) assertion that more than one-half of the variance in aggressive behavior is accounted for by genes, and contrast that conclusion with empirical evidence that measures of individual differences in children's aggression are only modestly correlated across home and school settings ( r's of about 0.2; Hope, Bierman, & Conduct Problems Prevention Research Group, 1998), across different peer targets ( r's of 0.1; Hubbard, Dodge, Cillessen, Coie, & Schwartz, 2001), across types of settings such as play versus classrooms ( r's of 0.3; Dodge, Coie, & Brakke, 1982), and across time ( r's of 0.5; Coie & Dodge, 1983). Shouldn't these low cross-setting correlations indicate the strong influence of the environment on behavior? Scarr's conclusion was based on the premise that cross-setting and cross-time differences reflect "error variance" that should be resolved by first aggregating measures across source, setting, and time before a test of genetic versus early family environment is conducted. The implication of this aggregation is that, according to the traditional behavior-genetic view, the fundamental gene-environment test concerns the relative proportion of variance accounted for by genes versus early family environment on life-enduring behavior scores that disregard effects of setting, peer target, time, and transient environmental influences. All of the latter effects are assumed to be error variance. In such a test, genes are indeed shown to exert an important impact.

These assumptions inherent in the behavior-genetic test are simply not consistent with a contemporary view of how the environment exerts an impact on behavior. Virtually no environmental theory posits that early family interaction causes effects on aggressive dispositions that will endure forever, no matter what later environmental or maturational influences occur. Rather, the fundamental nature of environmental theory is that social influences alter behavior patterns only as long as those social influences are still present. When the social influences change, the behavior will change (after a delay, in order for the organism to recalibrate the contingencies of the environment). Social experiments of an A-B-A-B design are premised on the transient nature of environmental impacts. Such a premise does not diminish the importance of the environment; in contrast, it heightens the continuing importance of the environment across the life span.

Consider as a thought experiment a behavior-genetic study in which monozygotic and dizygotic twins of many different ages are sampled from multiple cultures (including the United States, where handgun homicide rates are a thousand times higher than in some European countries, as well as European and Far Eastern countries) and from multiple time points in history (including contemporary times as well as times before guns were invented). The behavior-genetic test partitions variance into three components: genetic, non-shared family environment (i.e., the differences between persons within the same family), and shared family environment (i.e., differences across families). If the outcome variable is handgun homicide, then no doubt the effect of shared family environment would be over 90%, because gun laws, the invention and availability of handguns, and social constraints on access to guns exert a large impact on handgun homicide that is shared by members of the same family but varies across secular time and culture.

Why does this obvious effect of the environment not bring down the size of the genetic effect in actual empirical studies? Every behavior-genetic study "controls" for environmental variation that is due to secular time and culture (and a host of other environmental factors) by restricting the sample to a single culture or a single point in history. Furthermore, the outcome variable is rarely a score with such strong ecological validity as handgun homicide. Instead, the outcome variables are ironically so context-calibrated that they virtually eliminate context effects (e.g., a parent's rating of a child's level of aggression).

Several conclusions can be drawn from this debate. First, the gene-environment test depends on whether we are interested in understanding specific behavioral events (e.g., Johnny hitting Daryl on the playground, or Judy shooting Delilah at a party) or immutable personality propensities (e.g., aggressiveness or extraversion). By studying discrete acts or behavior scores that are so dependent on context (e.g., a law prohibiting handgun ownership), we will privilege the effect of the environment. By dismissing transient environmental variation as error variance, we will privilege the effect of genes.

Second, the magnitude of the effect of genes or the environment on individual differences will vary greatly as a function of the composition of the sample being studied, a point well illustrated by the empirical analyses of Stoolmiller (1999). If the sample includes only a narrow range of environmental differences, such as, say, a sample of Scandinavians (which constitute the majority of studies in behavior genetics because of the ease of tracking children across time in this society that keeps splendid permanent records of children's where-abouts), then the estimate of genetic effects will be relatively large. In contrast, one could constitute a sample that maximizes environmental differences to yield a relatively large environmental effect. The proportion of variance accounted for by genes is a description of the sample being studied, with relatively little generalization beyond that sample.

So what is the appropriate sample for these studies? Perhaps we could contemplate the world's entire population. But the population is a moving target. The third assertion being made here is that the human species has evolved across generations to maximize biological potential (i.e., the gene pool), environmental affordances (e.g., gains in nutrition and shelter), and the biological-environmental fit for survival. The result may be that the human species as a species has become more influenced by the environment than ever before and than other species (e.g., human infants today are born more dependent on the mother for survival than any other species), but that because of improvements in, and narrowing of, the minimal environmental standard (which generally holds outside of third-world countries), individual differences in behavior reflect genes to a greater extent than previously. The search for absolute answers to the question of how much behavior is accounted for by genes versus the environment is a futile exercise.

Gene-Environment Interaction Effects

Scarr (1992) asserted yet another of the important insights in this debate when she argued that the environment exerts its effect only at the most extreme end of environmental deprivation (e.g., physical abuse). Her intent was to point out the minimal role of the environment, but this assertion grants an exception to the dominance of the gene and illustrates one kind of gene-environment interaction, namely, that genes might have a larger or smaller effect at different points in the environmental continuum. And so, a body of recent studies has revealed that the environment might well exert a stronger effect on poor children than on children in the middle class ( National Research Council, 2000).

This discovery is one example of the broader gene-environment interaction effect. Although it was posited decades ago (e.g., Mischel, 1973), recent discoveries have revealed the enormous power of this effect in describing behavior. Among the most remarkable of these findings are those by the team of Caspi and Moffitt. Following children from the Dunedin Study, they discovered that genetic vulnerability (i.e., an inherited MAOA deficiency) for conduct disorder is expressed only in the context of the experience of physical abuse ( Caspi et al., 2002). Likewise, the impact of the experience of physical abuse on later conduct disorder occurs only among those children who are at genetic risk for this disorder.

Jaffee et al. (in press) recently applied similar concepts in the E-Risk Study of 1,116 twin pairs in Great Britain. They used zygosity status (monzygotic versus dizygotic) and the conduct disorder status of one's twin to grade the genetic risk level of a child, along with evaluations of a history of physical maltreatment, to determine that the effect of physical maltreatment on risk for conduct problems is strongest among those at high genetic risk. The experience of maltreatment was associated with an increase of 2% in the probability of a conduct disorder diagnosis among children at low genetic risk for conduct disorder but an increase of 24% among children at high genetic risk.

Dodge et al. (2003) demonstrated a similar effect in a different context in a sample of 585 boys and girls followed prospectively from preschool through middle school. They examined the effect of the environmental experience of being chronically rejected by one's peer group during early elementary school on growth in aggressive behavior problems by the beginning of middle school. Peer rejection is a major social stressor experienced by 10 to 15% of the school population. They found that this experience was associated with growth in aggressive behavior only among the subgroup of children who had in early life displayed difficult temperamental behavior patterns. Children without that (presumably biologically mediated) propensity did not react to the stressor of social rejection in an aggressive manner. Again, this interaction effect suggests that environmental effects occur within specific biological contexts and that genetic effects depend on environmental circumstances. These demonstrations of true gene-environment interaction effects render the debate about the relative importance of genes versus the environment moot: both factors are undeniably crucial in understanding how behavior unfolds across development.

The Dynamic Relation Between Biology and the Environment

Another major discovery is the understanding of how biological status and the environment are not static entities unrelated to each other but, rather, operate in dynamic tandem across development ( Dodge, 1990). Two concepts are worth highlighting.

First, one of the great insights of developmental psychology is that the environment acts in response to a child's biological affordance ( National Research Council, 2000). A young child who displays an aggressive disposition will likely be met with a different environmental response than a child with a calm disposition. In healthy environments, the societal response has evolved to compensate for a child's vulnerabilities through extra support, scaffolding, and protection. Thus, vulnerable children may receive extra attention and nurturance. Often, however, the social response may well be to act in a way that mediates the very problematic outcome for which the child is vulnerable. A child with a prickly temperament may incite parents to react with physical abuse or peers to react with social rejection. These environmental experiences, in turn, exacerbate the child's behavioral difficulties and potentiate problem outcomes ( Dodge & Pettit, 2003). Some behavior geneticists have used such findings to conclude that the environment is incidental in the developmental path of a genetically vulnerable child, whose destiny is inevitable. This conclusion makes no more sense than concluding that the environmental occurrence of nicotine ingestion through cigarette smoking is incidental to the development of lung cancer in an individual who is genetically primed to like and become addicted to cigarettes. The environment is responsive to one's biological dispositions and may well potentiate morbid outcomes.

Second, not only is the environment responsive to biological dispositions, but biological dispositions evolve in response to environmental inputs. De Bellis (2001) has used MRI technology to demonstrate that young children's brain volume and structure are altered as a result of maltreatment. Pollak, Klorman, Thatcher, and Cicchetti (2001) have used priming paradigms and electrophysiological recording to demonstrate that children who have been physically abused become perceptually and psychophysiologically ready to attend to hostile facial displays. This acquired biological disposition mimics the genetically based neurological vulnerability displayed by some children to act impulsively and to display attention deficits, and it may well exacerbate behavioral problems. In this case, the psychophysiological reaction to the environmental experience of physical abuse may potentiate the effect of abuse on long-term outcomes.

Thus, the environment and one's biologically based dispositional tendencies may dance with each other across development to lead, in some cases, to compensate for each other's vulnerabilities, and, in other cases, to potentiate each other's effects.

The Gene-Environment Fit

The gene-environment story gets considerably more complicated when we consider the possibility that the human species has biologically evolved to be especially responsive to differences in the environment that one experiences. Belsky, Steinberg, and Draper (1991) have posited the notion that children are born with the capability to alter their biological development by reading the type of nurturant environment that they experience in early life. If the environment is threatening, nonsupportive, and signaling an early demise, then the child may accelerate biological maturation, including puberty, in order to pass along one's genes to the next generation before one's demise. In contrast, if the environment is safe, nurturant, and signaling a long life, then biological maturation may be slowed in favor of higher-quality outcomes and better choices in mating partners for procreation. Evidence has accumulated that is consistent with, but hardly conclusive of, this perspective ( Ellis et al., 2003).

Most importantly, this research has led to the concept of the gene-environment fit, the notion that some children may flourish under one set of environmental conditions but flounder under another set, whereas other children may flounder under the first set while flourishing under the second set. Consider the temperamentally exuberant child who has creative ideas but difficulty holding them back from expression. This child might well flounder in a school environment that requires conformity to a predetermined set of rules; the same child could flourish if exposed to challenging tasks and left alone to explore. Bates, Pettit, Dodge, and Ridge (1998) found that children with difficult temperaments responded to lax parenting with growth in aggressive behavior problems but responded to structured parenting with acceptable behavioral outcomes. These findings suggest that parenting intervention programs should not be directed in an identical manner toward all families but should, instead, be targeted toward specific kinds of families based on fit.

Similar principles apply to children's learning styles. Levine (2002) has found that children with learning disabilities can achieve extraordinary outcomes that one might not expect based solely on a genetically driven assessment of intelligence. These children, however, demonstrate differential responsiveness to various educational interventions as a function of child-specific learning styles. Not all interventions will be equally effective with all children. The task for practitioners is to assess each child's profile of abilities and learning styles and then match interventions to each child's profile.

Transforming Research, Practice, and Policy

The discoveries of the past decade have important implications for research, practice, and public policy over the next decade. First, researchers should turn their attention to identifying and understanding the particular ways in which genes and environments interact and transact in particular domains. The nature-nurture debate has been transformed by the concepts described by the National Research Council in its seminal volume, Neurons to Neighborhoods. The search for the gene-environment fit is on.

Second, in order to identify strengths and deficits in behavior or learning, practitioners must assess not only an individual child but also the environment in order to identify the child-environment fit that is optimal for development. Psychological assessments must become environmental assessments.

Finally, public policy must shift away from its current main-effects dual foci on early selection of the best and brightest for privileged status and environmental enrichment for all disadvantaged children. Instead, public policy must begin to focus on matching children with the environments in which they will flourish. Education policy must allow for more individualization in curriculum planning. Early childhood care policy must be tailored toward different kinds of family circumstances. Mental health policy must encourage greater matching of interventions with child characteristics. Health policy, too, must match children with diets and exercise regimens that will optimize healthy outcomes for all children.

Although these reforms will make the world a more complicated place, they will maximize human potential. This legacy is indebted to the contributions of developmental psychology.

Acknowledgments

The author acknowledges the support of a Senior Scientist Award from the National Institute on Drug Abuse.

References

Jaffee SR, Caspi A, Moffitt TE, Dodge KA, Rutter M, Taylor A, Tully LA. Nature x nurture: Genetic vulnerabilities interact with child maltreatment to promote conduct problems. Development and Psychopathology. in press. [[PMC free article] [PubMed] Google Scholar]

National Research Council. From neurons to neighborhoods: The science of early childhood development. National Academies Press: Washington, DC; 2000. [[PubMed] Google Scholar]

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The Nature-Nurture Debate and Public Policy

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The contentious nature-nurture debate in developmental psychology is poised to reach a rapprochement with contemporary concepts of gene-environment interaction, transaction, and fit. Discoveries over the past decade have revealed how neither genes nor ...

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The nature vs. nurture debate is the long-standing argument over whether heredity (nature) or environment (nurture) plays a greater role in developing human characteristics and behaviors.
Nature refers to the biological characteristics we are born with, including genetic predispositions toward certain traits. In contrast, nurture includes external influences that shape us, such as culture, relationships, and everyday experiences.

For example, when it comes to personality development, some people believe that genetics play a stronger role than environmental factors; this would be considered a nature-focused perspective.

Others may view the environment as more important. In this case, a nurturing upbringing could help individuals develop their personalities. Therefore, both sides can have valid arguments for their respective positions in the debate.

The Nature Perspective
In the context of the nature vs. nurture debate, nature refers to biological heredity and genetic predispositions inherited by individuals from their parents at birth.
Buheji (2018) states that:

"in the "nature vs. nurture" debate, nature refers to an individual's innate qualities (nativism)" (p. 221).

This includes physical characteristics such as eye color, facial features, personality traits, and behavioral tendencies.

Genes determine the unique physical characteristics of each individual while also influencing psychological and social behavior.

Some research implies that roughly 50% of an individual's personality and disposition are pre-determined by genetics (Bouchard & Loehlin, 2001).

However, Krueger and colleagues (2008) state that the interplay between gene-environment interactions has a consequential effect on one's character traits. Hence, the heritability of personality isn't always precisely 50%.

So, nature is the hereditary and genetic characteristics pre-determined at birth and influence a person's behavior.

The Nurture Perspective
Nurture, in the context of the nature vs. nurture debate, is used to describe environmental factors that influence an individual's development.
According to Coon and Mitterer (2014), nurture:

"...refers to the sum of all external conditions that affect a person" (p. 100).

This includes a variety of influences such as parenting style, educational experiences, cultural background, and exposure to different environmental conditions over time.

While "nurture" may naturally invoke ideas of childhood and parental care, environmental components and life experience can shape human mental, emotional, and physical health throughout their lives (Harsha et al., 2020).

For example, lifestyle choices have been found to impact a person's risk for developing certain diseases and their level of immunity against illness.

Furthermore, addiction susceptibility can be impacted by environmental factors such as peer group that has been observed throughout an individual's life (Ducci & Goldman, 2012).

Simply, nurture is an umbrella term for any environmental influences that shape the development of a person's mental, physical, and emotional health.

Examples of Nature vs Nurture

Nature Examples

Eye color: A person's eye color is determined by their genetic makeup and inherited from their parents.

Height: As with eye color, height is a physical trait that is determined by a person's genes and largely determines an individual's adult height.

Risk of D iseases: A person's risk for developing certain diseases can be partially attributed to their genetic predisposition for that illness and influenced by lifestyle factors and personal environment.

Immune S ystem F unctionality: Genetic predisposition plays an important role in determining an individual's resistance to disease through the strength of their immune system. However, lifestyle choices can also influence this trait over time (e.g., diet and exercise).

Hair Color: Hair color is determined by genetic factors. Recessive genes, like the red hair gene, generally have to be present in both parents for the recessive gene to become dominant.

Balding: Going bald is an inherited trait. Some groups - such as male British Anglo-Saxons - are more likely to go bald in their 30s than the average.

Adrenaline response: An individual's ability to react quickly in dangerous situations-their "fight or flight" response-tends to be innate in all of us.

Nurture Examples

Ethics and Parenting style: An individual's upbringing and the parenting style they are exposed to can shape their behavior, emotional reactions, and psychological outlook throughout life.

Linguistic Determinism Theory: In this theory, the language we are taught as a child will determine the ways we think and interact with the world. It goes some way to explaining how people of differing language groups may have differing values and belief systems.

Values and Cultural background: Depending on their cultural background, different individuals may be exposed to different values and belief systems, which can impact their attitudes toward certain issues or topics/ideas/beliefs.

Anxiety and Exposure to T rauma: Experiences with violence or traumatic events can have long-term effects on an individual's psychology which could manifest outwardly as symptoms of anxiety or difficulty coping under pressure in later stages of life.

Positivity and Social E nvironment: The people an individual interacts with can either positively or negatively affect their development. Individuals need to surround themselves with positive influences while avoiding those that might lead them down the wrong path in life.

Relationship E xperiences and Sense of Security: Positive relationships throughout a person's life will tend to improve outlook and well-being. In contrast, unhealthy relationships could leave long-term psychological damage that might need professional help before it can be addressed adequately by an individual suffering firsthand.

Nature and Nurture Examples

Personality traits: The role of genetics (nature) in determining personality traits, such as extraversion or conscientiousness is balanced against the influence of upbringing and life experiences (nurture).

Aggression: There is debate over whether aggressive behavior is primarily influenced by genetic factors (nature) or by environmental factors, such as upbringing, social learning, and exposure to violence (nurture).

Athletic ability: The role of genetics (nature) determines a lot of our natural talent in sports but the importance of training, motivation, and exposure to physical activity (nurture) takes us the rest of the way.

Musical talent: Musical ability may be affected by genetic predisposition (nature) but also environmental factors, such as exposure to music at a young age, education, and practice (nurture).

Attachment styles: It is debatable whether a person's attachment style (secure, anxious, or avoidant) is impacted by genetics (nature) versus the influence of early childhood experiences and caregiver relationships (nurture).

Empathy and emotional intelligence: The capacity for empathy and emotional intelligence is debatably determined by both genetics (nature) and the result of upbringing, social exposure, and life experiences (nurture).

Spiritual beliefs: Theological determinism holds that god has pre-selected his chosen people who will be true believers (nature) while others think that belief in god is a choice and we must raise our children to maintain a belief in god (nurture).

Learning styles: In the 1980s, there was extensive debate over whether preferred learning styles, such as visual, auditory, or kinesthetic, are determined by genetic factors (nature) or influenced by educational experiences and personal development (nurture). Today, most education theorists believe that learning preferences are based on nurture over nature.

Addiction susceptibility: Scientists have identified genes related to addiction susceptibility, even though this trait is also heavily influenced by the environment (Ducci & Goldman, 2012).

Intelligence: Education can significantly impact traits such as intelligence levels and knowledge base, with certain experiences inspiring curiosity or creativity in individuals later in life.

Origins of Nature vs. Nurture Debate
The debate surrounding the extent to which human development is influenced by nature (heredity) or nurture (environmental factors) has been around since ancient times.
Plato, the renowned Greek philosopher, argued that beneficial traits in humans were attributable to both nature and nurture. He believed people could adapt to external occurrences throughout their lifetime (Englander, 2010).

However, his mentor Socrates leaned more towards genetics as the primary factor of human development - a notion known as Nativism, which was coined by both philosophers together.

In the late 1800s, Charles Darwin's theory of evolution and Sir Francis Galton's article "Hereditary Talent and Character" sparked a resurgence in interest in this topic (Galton, 1865)

So, Galton (1865) suggested hereditary influences to be at least as important as the environment when determining an individual's outcomes in life.

The debate continued through subsequent decades, with psychologist John B. Watson's revolutionary suggestion that environment-what he called "nurture"-was more important than hereditary factors or biology (Herrnstein, 1998).

In recent years, researchers have realized that both internal (genetic) and external (environmental) factors play a role in how individuals develop physically and psychologically.

As such, most experts now subscribe to an approach that looks at how both genetic inheritance and environmental influences work together throughout life to shape each person's unique character traits and behaviors.

The Role of Epigenetics in the Nature vs. Nurture Debate
Epigenetics is the study of changes in gene expression caused by environmental factors, such as diet and exposure to toxins, without altering the underlying sequences of DNA.
It is an emerging field of research that has been gaining prominence in recent years as scientists try to uncover how and to what extent the environment can shape genetic expression (Harvard University, 2019).

Epigenetic influences are now considered a significant factor in the nature vs. nurture debate, particularly in how individuals develop physically and psychologically throughout life.

Evidence suggests that epigenetic mechanisms can be used to modulate gene expression depending on the environment, thus having a direct influence on an individual's characteristics and behaviors (Harvard University, 2019).

This means that while both genetics and environment may play a role in determining an individual's outcomes in life, epigenetics provides an additional layer of complexity by allowing environmental factors to interact with gene expression.

Conclusion

Nature vs. nurture is a decades-old debate that continues to be studied in various fields.

Nativists state that genetics play a major role in determining characteristics and behaviors. For example, a person may have inherited certain traits from their family.

However, empiricists suggest that external factors, such as upbringing and lifestyle choices, can also have a significant influence.

From ancient philosophers to modern-day scientists, this debate has gone through various iterations and continues to evolve today with the introduction of epigenetics.

More recently, epigenetics have emerged as a key factor in the debate. Its mechanisms can be used to modulate gene expression depending on the environment, thus having a direct influence on an individual.

So, it appears that both nature and nurture are important factors in determining an individual's outcomes in life.

References

Bouchard, T. J., & Loehlin, J. C. (2001). Genes, evolution, and personality. Behavior Genetics, 31(3), 243-273. https://doi.org/10.1023/a:1012294324713

Buheji, M. (2018). Understanding the power of resilience economy. Mohamed Buheji.

Coon, D., & Mitterer, J. O. (2014). Psychology: A journey. Wadsworth/Cengage Learning.

Ducci, F., & Goldman, D. (2012). The genetic basis of addictive disorders. Psychiatric Clinics of North America, 35(2), 495-519. https://doi.org/10.1016/j.psc.2012.03.010

Englander, M. (2010). The nature and nurture of learners. AuthorHouse.

Galton, F. (1865). Hereditary talent and character. University of Bristol Library.

Harsha, N., Ziq, L., Lynch, M. A., & Giacaman, R. (2020). Assessment of parental nurturing and associated social, economic, and political factors among children in the West Bank of the occupied Palestinian territory. BMC Pediatrics, 20(1). https://doi.org/10.1186/s12887-020-02317-0

Harvard University. (2019). What is epigenetics? The answer to the nature vs. nurture debate. Center on the Developing Child at Harvard University; Harvard University. https://developingchild.harvard.edu/resources/what-is-epigenetics-and-how-does-it-relate-to-child-development/

Herrnstein, R. J. (1998). Nature as nurture: Behaviorism and the instinct doctrine. Behavior and Philosophy, 26(1/2), 73-107. https://www.jstor.org/stable/27759383

Krueger, R. F., South, S., Johnson, W., & Iacono, W. (2008). The heritability of personality is not always 50%: Gene-environment interactions and correlations between personality and parenting. Journal of Personality, 76(6), 1485-1522. https://doi.org/10.1111/j.1467-6494.2008.00529.x

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Viktoriya Sus (MA) and Peer Reviewed by Chris Drew (PhD)

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The nature vs. nurture debate is the long-standing argument over whether heredity (nature) or environment (nurture) plays a greater role in developing human

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Isabella

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Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder encompassing severe deficits in social communication and language development, and associated with repetitive, stereotypic behaviors. It is estimated that as many as 1 in 150 children in the United States are affected (Centers for Disease Control and Prevention, 2007).

Over the past decade, we have witnessed remarkable scientific advancements in our ability to explore the origins and manifestations of autism, using tools such as genome-wide microarray analyses, functional neuroimaging and automated eye tracking. Yet, despite these innovations, we have failed to uncover a core psychobiological deficit for autism. Without such an understanding, treatment options are limited to various combinations of child-directed therapy, with minimal data supporting effectiveness (Ospina et al., 2008). With the dramatic rise in the number of children diagnosed with autism (Blaxill, 2004) comes an escalating burden for schools, governments and society to provide intensive and costly services. Clearly, understanding the etiology of autism is of paramount importance.

The Etiology of Autism - Nature vs. Nurture

Over the past 60 years, the pendulum of public and scientific opinion on the etiology of autism has swung between two extreme positions: (1) that autism is caused by some specific genetic abnormality, spawning a search for the "autism gene", and (2) that autism is the result of some specific environmental factor or condition, including a "lack of maternal warmth" (Kanner, 1949). Although the etiology of autism has remained elusive, the evidence to date has strongly refuted both of these extreme positions.

As one of the first to systematically examine and describe a cohort of children with autism, Kanner hypothesized that these children were both genetically predisposed to develop autism, but also affected by parenting behavior. In his original 1943 paper, he stated that they "come into the world with innate inability to form the usual, biologically provided affective contact with people", while he questioned "whether or to what extent [parenting behaviors and characteristics] contributed to the condition of the children" (Kanner, 1943). Based on his observations of the families of children with autism, he later suggested that autism may be caused by a "genuine lack of maternal warmth" (Kanner, 1949). However, this idea was directly confronted by a psychologist named Bernard Rimland (who was also the parent of an ASD child) in his book, " Infantile Autism: The Syndrome and its Implications for a Neural Theory of Behavior" (Rimland, 1964). Herein he proposed a purely biological mechanism for the etiology of autism.

Nature: The Contribution of Genetics

Over subsequent years, epidemiological studies have pointed to a genetic etiology of autism, with up to 60% concordance in monozygotic twins compared with ∼5% for dizygotic pairs (Bailey et al., 1995). Nevertheless, affected monozygotic twins did not exhibit similar autistic characteristics, any more so than dizygotic twins (Le et al., 1996), implying that non-genetic or epigenetic factors were also likely to be important.

Today, with the availability of genome-wide array analyses, multiple genetic markers of autism susceptibility have been identified, such as genes encoding for neuronal cell-adhesion molecules (Wang et al., 2009) and copy number variations in surrounding regions (Glessner et al., 2009). However, these factors appear to explain only a small degree of variance (Geschwind, 2008; Sutcliffe, 2008). Other rare genetic disorders, such as Fragile X syndrome and tuberous sclerosis, have been associated with a higher rate of autism, although each possesses fundamentally different genetic abnormalities (Levitt and Campbell, 2009). One recently discovered functional class of autism-associated genes is regulated by neuronal activity, suggesting that both genetic variation and experience may contribute to the development of autism (Morrow et al., 2008). Thus, current models propose that multiple genetic, epigenetic and environmental factors may contribute to the etiology of autism (Geschwind, 2008).

Nurture: The Contribution of Social Environment

Even before the careful descriptions of ASD patients were published by Kanner and Asperger, isolated cases were reported of children exhibiting autistic features, who had been exposed to severe trauma or deprivation (Wolff, 2004). Harlow's studies of rhesus monkeys exposed to severe maternal deprivation also revealed behavioral characteristics resembling that of autism (Harlow and Harlow, 1972). In 1999, "quasi-autistic" traits were described in up to 12% of Romanian orphans exposed to severe deprivation, who were later adopted in the UK, with symptoms related to the age of adoption (Rutter et al., 1999). At age 4, these children were clinically indistinguishable from children with "typical" autism, although differences in behavior and response to treatment emerged over time (Rutter et al., 2007). Rutter and colleagues proposed that "social privation might also impair developmental programming for aspects of psychological functioning relevant to the genesis of autism".

Many congenitally blind children also exhibit characteristics of autism, to varying degrees. A spectrum of autistic features has been observed in visually impaired children (Hobson and Bishop, 2003), with autistic features significantly correlated with severity of blindness and mental retardation (Mukaddes et al., 2007). This leads to the question: are there mechanisms which may account for the observed relationship between sensory deprivation, congenital blindness and autism?

Face Processing, Oxytocin and Autism

Both Dawson ( 2008) and Schultz ( 2005) have hypothesized that basic deficits in social perception may underlie many of the other developmental and behavioral abnormalities seen in autism. They hypothesize that a set of defining experiences early in development may critically affect the development of multiple neural systems. Just as visual deprivation during a critical period of development may result in long-term visual impairment (Wiesel and Hubel, 1965), it is proposed that social deprivation - either externally or internally derived - may contribute to impairment in social development.

While face processing is a key factor in the development of social perception, it is severely impaired in autistic children. Numerous studies have noted face processing deficits using ERP (Dawson et al., 2005b), as well as an impaired ability to recognize faces (Klin et al., 1999) and to fixate on the eyes of others (Jones et al., 2008). Functional MRI studies have demonstrated reduced activation of the fusiform face area when viewing or discriminating faces of unknown adults (Pierce and Redcay, 2008; Schultz, 2005). While infants possess an innate perceptual bias for face-like shapes, the capacity to distinguish facial features develops during the first year of life (Cassia et al., 2006; Gliga and Csibra, 2007). It is proposed that some cases of ASD may result from a deficit in exposure to contingent, socially responsive facial expressions during a sensitive period of social development.

Oxytocin (OT), a neuropeptide associated with social memory and learning, enhances direct eye gaze and the ability to identify and remember faces, as seen in blinded placebo-controlled trials (Guastella et al., 2008; Savaskan et al., 2008). OT receptor expression also appears to be programmed by early life experience via epigenetic mechanisms (Champagne et al., 2001, 2006), with decreased expression seen in the brains of animals who received lower levels of contingent maternal care in infancy. OT deficits in humans have also been implicated in autism, with reduced peripheral OT levels observed in autistic subjects (Green et al., 2001; Modahl et al., 1998). Furthermore, intravenous OT produces a reduction in stereotypic behaviors in adult ASD subjects (Hollander et al., 2003). Together, these studies suggest that OT may play an important role in promoting social perception, while deficits may be associated with the development of autism.

Conclusions: Nature and Nurture?

As originally observed by Kanner, and confirmed in numerous recent studies, parents of autistic children often exhibit similar characteristics, including face processing deficits, aloofness, behavioral rigidities, and pragmatic language deficits (Dawson et al., 2005a; Piven et al., 1994, 1997). While these characteristics have generally been ascribed to a genetically based "broad autism phenotype", it is also possible, as Kanner first proposed, that "the patient, endowed with an innate disability to relate to people, is further influenced adversely by the parents' emotional detachment" (Kanner, 1965). Is it possible, for example, that the parents' face processing deficits may be causally linked to the deficits seen in their children? Furthermore, could "institutionalization" of infants, in the form of prolonged early non-parental care, be an additional risk factor for autism? As our understanding of epigenetics evolves, the answers may lie in how the social environment influences gene expression and social development.

Thus, despite detours along the way, we return to the original observations of Kanner to propose that the true etiology of autism may incorporate both nature and nurture - genetically determined predispositions and the cumulative effects of exposure to adverse or atypical social environments.

References

Centers for Disease Control Prevention. (2007). Morbidity and Mortality Weekly Report. Surveillance Summaries, Vol. 56 (No. SS-1). Atlanta, GA, Coordinating Center for Health Information and Service, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services.

Harlow H. F., Harlow H. K. (1972). The affectional systems. In Behaviour of Non-human Primates, Schrier A., Harlow H. F., Stollnitz F., eds. New York, Academic Press [Google Scholar]

Kanner L. (1943). Autistic disturbances of affective contact. Nerv. Child 2, 217-250 [Google Scholar]

Kanner L. (1949). Problems of nosology and psychodynamics of early infantile autism. Am. J. Orthopsychiatry 19, 416-426 [[PubMed] Google Scholar]

Rimland B. (1964). Infantile Autism: The Syndrome and its Implications for a Neural Theory of Behavior. New York, Appleton-Century-Crofts [Google Scholar]

Wiesel T. N., Hubel D. H. (1965). Comparison of the effects of unilateral and bilateral eye closure on cortical unit responses in kittens. J. Neurophysiol. 28, 1029-1040 [[PubMed] Google Scholar]

Articles from Frontiers in Behavioral Neuroscience are provided here courtesy of Frontiers Media SA

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The Elusive Etiology of Autism: Nature and Nurture?

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Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder encompassing severe deficits in social communication and language development, and associated with repetitive, stereotypic behaviors. It is estimated that as many as 1 in 150 children in the United States are affected (Centers for Disease Control and Prevention, 2007).

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sorry wrong one!!

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Does Nature or Nurture Determine Your Personality?

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Understanding the interplay between inherited temperament and environment.

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Nature vs Nurture | Genetics | Biology | FuseSchool

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Isabella- principles of nurture defined

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We offer schools a range of tools and resources to address pupils' social, emotional and mental health needs. The aim isn't for teachers to focus on the children with the greatest needs, but to develop an inclusive, whole-class approach that allows them to access all their pupils.

Our nurturing tools and resources can be used throughout the school day (in the classroom or in small groups) to help children develop the skills they need to engage with their learning and make the most of their time at school.

These strategies could include:

Making time for social and emotional learning, either during targeted PSHE lessons or by embedding it throughout the curriculum.

Giving pupils the opportunity to practice their social and emotional skills, for example by encouraging them to work in pairs and groups.

Modelling good social and emotional skills themselves, when interacting with pupils and other staff members.

Monitoring the social and emotional wellbeing of the whole class, using assessment tools like The Boxall Profile®.

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What is nurture? Discover more about the Six Principles of Nurture

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Discover what nurture is all about: helping children develop vital social skills, confidence and self-esteem, and becoming ready to learn.

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What is Nature? | Ralph Waldo Emerson’s “Nature”

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Nature vs. nurture is the age-old debate about whether environment or genetics plays a larger role in determining a person’s characteristics. Learn about examples here.

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The University of Texas Permian Basin | UTPB

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New parents tend to pull out all the stops to raise their children in a nurturing environment, painting nursery walls in subdued hues, praising their child's first steps and words, and reading a favorite storybook as their child drifts off to sleep. Chances are that there's a copy of "What to Expect When You're Expecting" open on someone's nightstand right now. However, even the most meticulously laid plans often do little to alter the course of nature, and parents may find their newborn's behavior influenced more by biology than their well-meaning care.

The nature versus nurture debate has endured for thousands of years, since Ancient Greeks pondered the origins of personality. Who are we? Are we products of our genome (nature) or environment (nurture)? These questions strike at the very heart of psychology, and to answer them, we'll be taking a closer look at these diametrically opposed ideas.

Nurture

English philosopher John Locke compared the mind at birth to a tabula rasa, or blank slate, upon which our experiences imbue reason and knowledge. This is "nurture," the idea that a child's environment determines whom they turn out to be.

A report published by the National Academies of Sciences, Engineering, and Medicine (NASEM) affirms that informed parents are more likely to have positive interactions with their children in ways that support healthy development. By showing warmth, being responsive, and promoting other evidence-based practices, parents can improve outcomes relating to their child's emotional, behavioral, cognitive, and social skills. Conversely, children can experience devastating, long-term changes as a result of neglect and abuse, ranging from the development of antisocial behaviors to the stunting of their growing minds.

A person's environment is most impactful during their early years, when their brain has yet to fully develop and their experiences are shaped entirely by their home life. There's no doubt that nature plays a critical role in deciding the trajectory of our lives. The question is, how much of our behavior is inherited?

Nature

When people talk about heredity, they almost exclusively refer to their physical traits. They might say, "I have my mother's eyes" or "my father's nose," but the characteristics we inherit from our parents are more than skin deep.

The determinants of your most prominent traits are found in your chromosomes, with each of your parents contributing half of their chromosomes to the 23 pairs found in your cells. Chromosomes are composed of segments of DNA called genes. Think of genes as blueprints, carrying instructions that determine your every biological trait, including the color of your hair, eyes, and skin. Moreover, your personality, intelligence, and mental health can also be attributed, at least in part, to your genetic makeup.

Two of a Kind

Scientists have taken a novel approach to testing the effects of heredity on personality: studying twins. Identical twins share the same genes, whereas fraternal twins share half of their genes, like other siblings. By contrasting the traits of identical and fraternal twins, scientists have been able to separate the influences of nature and nurture on human behavior. In a meta-analysis of the heritability of human traits, researchers looked at over 50 years of twin studies, compiling evidence from over 2,000 publications reporting on a combined 17,804 traits and 14,558,903 twins. They found that the heritability of human traits, including temperament and personality functions, is about 50%. To put it simply, half of our unique personalities can be attributed to heredity, or nature.

Ending the Debate

Has the revelation that genetics accounts for half of our mental and physical traits-and that both sides hold equal sway over our personalities-put an end to the nature versus nurture debate? Not quite. This debate has proven more nuanced than previously thought, particularly with the revelation that genetically driven behaviors shape our environments in the same way our environments shape us. For example, parents responding negatively to their child's antisocial behaviors may end up reinforcing those same behaviors. Complicating matters further are epigenetic changes that switch genes on and off. Traumatic experiences, in particular, can be passed on from one generation to the next. Complex factors like these continue to stoke the flames of this age-old debate.

More than opposing ideas, nature and nurture describe entwined influences that alter and build upon one another. While some argue that nature carries more weight because our genes, as opposed to our experiences, are set in stone, this is exactly why nurture is such an important concept. The family, society, and culture we're born into are random, but not all environmental factors are beyond influence, and something as simple as reading bedtime stories to a child could make a world of difference in who they grow up to be.

Discover Who You Are

Professionals in the field of psychology define themselves by their work, whether they're conducting research or administering care. This is a rewarding, albeit challenging, career path ideal for anyone interested in bringing fulfillment to their life and the lives of others. Nature versus nurture aside, you decide the course of your professional journey. And if you choose to become a psychologist, The University of Texas Permian Basin can help.

UT Permian Basin offers an online Bachelor of Arts in Psychology program that provides the foundational psychology knowledge you need to set yourself up for success in graduate school and beyond. Through our program, you'll gain a deeper understanding of empirical research, mental disorders, and the application of psychological principles in the real world. Virtual courses help ensure that you can participate when it's convenient for you, and although our program is entirely online and asynchronous, you'll receive the same distinguished degree as on-campus graduates. From its well-rounded curriculum to its experienced professors, our program offers everything you need to excel in a diverse range of psychology roles.

Ready to pursue your passion for psychology? Apply to our online BA in psychology program to gain the knowledge and skills needed to become the psychology professional you were born to be.

Sources:
https://blogs.scientificamerican.com/observations/in-the-nature-nurture-war-nature-wins/
https://www.theguardian.com/science/2015/mar/19/do-your-genes-determine-your-entire-life
https://www.psychologytoday.com/us/basics/nature-vs-nurture
https://www.nigms.nih.gov/education/fact-sheets/Pages/genetics.aspx
https://www.childwelfare.gov/pubpdfs/long_term_consequences.pdf
https://www.cdc.gov/genomics/disease/epigenetics.htm

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Nature vs. Nurture: The Debate Over Our Personalities | UT Permian Basin Online

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New parents tend to pull out all the stops to raise their children in a nurturing environment, painting nursery walls in subdued hues, praising their child's first steps and words, and reading a favorite storybook as their child drifts off to sleep.

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For nearly a century after the term "epigenetics" first surfaced on the printed page, researchers, physicians, and others poked around in the dark crevices of the gene, trying to untangle the clues that suggested gene function could be altered by more than just changes in sequence. Today, a wide variety of illnesses, behaviors, and other health indicators already have some level of evidence linking them with epigenetic mechanisms, including cancers of almost all types, cognitive dysfunction, and respiratory, cardiovascular, reproductive, autoimmune, and neurobehavioral illnesses. Known or suspected drivers behind epigenetic processes include many agents, including heavy metals, pesticides, diesel exhaust, tobacco smoke, polycyclic aromatic hydrocarbons, hormones, radioactivity, viruses, bacteria, and basic nutrients.

In the past five years, and especially in the past year or two, several groundbreaking studies have focused fresh attention on epigenetics. Interest has been enhanced as it has become clear that understanding epigenetics and epigenomics-the genomewide distribution of epigenetic changes-will be essential in work related to many other topics requiring a thorough understanding of all aspects of genetics, such as stem cells, cloning, aging, synthetic biology, species conservation, evolution, and agriculture.

Multiple Mechanisms

The word "epigenetic" literally means "in addition to changes in genetic sequence." The term has evolved to include any process that alters gene activity without changing the DNA sequence, and leads to modifications that can be transmitted to daughter cells (although experiments show that some epigenetic changes can be reversed). There likely will continue to be debate over exactly what the term means and what it covers.

Many types of epigenetic processes have been identified-they include methylation, acetylation, phosphorylation, ubiquitylation, and sumolyation. Other epigenetic mechanisms and considerations are likely to surface as work proceeds. Epigenetic processes are natural and essential to many organism functions, but if they occur improperly, there can be major adverse health and behavioral effects.

Perhaps the best known epigenetic process, in part because it has been easiest to study with existing technology, is DNA methylation. This is the addition or removal of a methyl group (CH ₃), predominantly where cytosine bases occur consecutively. DNA methylation was first confirmed to occur in human cancer in 1983, and has since been observed in many other illnesses and health conditions.

Another significant epigenetic process is chromatin modification. Chromatin is the complex of proteins (histones) and DNA that is tightly bundled to fit into the nucleus. The complex can be modified by substances such as acetyl groups (the process called acetylation), enzymes, and some forms of RNA such as microRNAs and small interfering RNAs. This modification alters chromatin structure to influence gene expression. In general, tightly folded chromatin tends to be shut down, or not expressed, while more open chromatin is functional, or expressed.

One effect of such processes is imprinting. In genetics, imprinting describes the condition where one of the two alleles of a typical gene pair is silenced by an epigenetic process such as methylation or acetylation. This becomes a problem if the expressed allele is damaged or contains a variant that increases the organism's vulnerability to microbes, toxic agents, or other harmful substances. Imprinting was first identified in 1910 in corn, and first confirmed in mammals in 1991.

Researchers have identified about 80 human genes that can be imprinted, although that number is subject to debate since the strength of the evidence varies. That approximate number isn't likely to rise much in years to come, writes a team including Ian Morison, a senior research fellow in the Cancer Genetics Laboratory at New Zealand's University of Otago, in the August 2005 Trends in Genetics. Others in the field disagree. Randy Jirtle, a professor of radiation oncology at Duke University Medical Center, and his colleagues estimated in the June 2005 issue of Genome Research that there could be about 600 imprinted genes in mice; in an October 2005 interview Jirtle said he's anticipating a similar tally for humans, even though the known imprintable genes of mice and people have an overlap of only about 35%.

Links to Disease

Among all the epigenetics research conducted so far, the most extensively studied disease is cancer, and the evidence linking epigenetic processes with cancer is becoming "extremely compelling," says Peter Jones, director of the University of Southern California's Norris Comprehensive Cancer Center. Halfway around the world, Toshikazu Ushijima is of the same mind. The chief of the Carcinogenesis Division of Japan's National Cancer Center Research Institute says epigenetic mechanisms are one of the five most important considerations in the cancer field, and they account for one-third to one-half of known genetic alterations.

Many other health issues have drawn attention. Epigenetic immune system effects occur, and can be reversed, according to research published in the November-December 2005 issue of the Journal of Proteome Research by Nilamadhab Mishra, an assistant professor of rheumatology at the Wake Forest University School of Medicine, and his colleagues. The team says it's the first to establish a specific link between aberrant histone modification and mechanisms underlying lupus-like symptoms in mice, and they confirmed that a drug in the research stage, trichostatin A, could reverse the modifications. The drug appears to reset the aberrant histone modification by correcting hypoacetylation at two histone sites.

Lupus has also been a focus of Bruce Richardson, chief of the Rheumatology Section at the Ann Arbor Veterans Affairs Medical Center and a professor at the University of Michigan Medical School. In studies published in the May-August 2004 issue of International Reviews of Immunology and the October 2003 issue of Clinical Immunology, he noted that pharmaceuticals such as the heart drug pro-cainamide and the antihypertensive agent hydralazine cause lupus in some people, and demonstrated that lupus-like disease in mice exposed to these drugs is linked with DNA methylation alterations and interruption of signaling pathways similar to those in people.

Substantial Changes

Most epigenetic modification, by whatever mechanism, is believed to be erased with each new generation, during gameto-genesis and after fertilization. However, one of the more startling reports published in 2005 challenges this belief and suggests that epigenetic changes may endure in at least four subsequent generations of organisms.

Michael Skinner, a professor of molecular biosciences and director of the Center for Reproductive Biology at Washington State University, and his team described in the 3 June 2005 issue of Science how they briefly exposed pregnant rats to individual relatively high levels of the insecticide methoxychlor and the fungicide vinclozolin, and documented effects such as decreased sperm production and increased male infertility in the male pups. Digging for more information, they found altered DNA methylation of two genes. As they continued the experiment, they discovered the adverse effects lasted in about 90% of the males in all four subsequent generations they followed, with no additional pesticide exposures.

The findings are not known to have been reproduced. If they are reproducible, however, it could "provide a new paradigm for disease etiology and basic mechanisms in toxicology and evolution not previously appreciated," says Skinner. He and his colleagues are conducting follow-up studies, assessing many other genes and looking at other effects such as breast and skin tumors, kidney degeneration, and blood defects.

Other studies have found that epigenetic effects occur not just in the womb, but over the full course of a human life span. Manel Esteller, director of the Cancer Epigenetics Laboratory at the Spanish National Cancer Center in Madrid, and his colleagues evaluated 40 pairs of identical twins, ranging in age from 3 to 74, and found a striking trend, described in the 26 July 2005 issue of Proceedings of the National Academy of Sciences. Younger twin pairs and those who shared similar lifestyles and spent more years together had very similar DNA methylation and histone acetylation patterns. But older twins, especially those who had different lifestyles and had spent fewer years of their lives together, had much different patterns in many different tissues, such as lymphocytes, epithelial mouth cells, intra-abdominal fat, and selected muscles.

As one example, the researchers found four times as many differentially expressed genes between a pair of 50-year-old twins compared to 3-year-old twins, and the 50-year-old twin with more DNA hypomethylation and histone hyperacetylation (the epigenetic changes usually associated with transcriptional activity) had the higher number of overexpressed genes. The degree of epigenetic change therefore was directly linked with the degree of change in genetic function.

Sometimes the effects of epigenetic mechanisms show up in living color. Changes in the pigmentation of mouse pup fur, ranging from yellow to brown, were directly tied to supplementation of the pregnant mother's diet with vitamin B ₁₂, folic acid, choline, and betaine, according to studies by Jirtle and Robert Waterland published in August 2003 (issue 15) in Molecular and Cellular Biology. The color changes were directly linked to alterations in DNA methylation. In a study forthcoming in the April 2006 issue of EHP, Jirtle and his colleagues also induced these alterations through maternal ingestion of genistein, the major phytoestrogen in soy, at doses comparable to those a human might receive from a high-soy diet. The methylation changes furthermore appeared to protect the mouse offspring against obesity in adulthood, although there are hints that genistein may also cause health problems, via additive or synergistic effects on DNA methylation, when it interacts with other substances such as folic acid.

Other Drivers of Change

Substances aren't the only sources of epigenetic changes. The licking, grooming, and nursing methods that mother rats use with their pups can affect the long-term behavior of their offspring, and those results can be tied to changes in DNA methylation and histone acetylation at a glucocorticoid receptor gene promoter in the pup's hippocampus. This finding was published in the August 2004 issue of Nature Neuroscience by Moshe Szyf, a professor in McGill University's Department of Pharmacology and Therapeutics, and his colleagues. In the same study, the researchers found that the effects weren't written in stone; giving the drug trichostatin A to older pups could help reverse the effects of poor maternal care received when they were younger. In the 6 June 2003 Journal of Biological Chemistry and the 23 November 2005 Journal of Neuroscience, Szyf and many of the same colleagues also demonstrated that giving the amino acid l-methionine to older pups could negate the benefits of high-quality maternal care received when they were younger.

Along with behavior, mental health may be affected by epigenetic changes, says Arturas Petronis, head of the Krembil Family Epigenetics Laboratory at the Centre for Addiction and Mental Health in Toronto. His lab is among the first in the world, and still one of only a few, to study links between epigenetics and psychiatry. He and his colleagues are conducting large-scale studies investigating links between schizophrenia and aberrant methylation, and he says understanding epigenetic mechanisms is one of the highest priorities in human disease biology research. "We really need some radical revision of key principles of the traditional genetic research program," he says. "Epigenetics brings a new perspective on the old problem and new analytical tools that will help to test the epigenetic theory." He suggests that more emphasis is needed on studying non-Mendelian processes in diseases such as schizophrenia, asthma, multiple sclerosis, and diabetes.

The past decade has also been productive in developing strong links between aberrant DNA methylation and aging, says Jean-Pierre Issa, a professor of medicine at The University of Texas M.D. Anderson Cancer Center. He presented information on aging and epigenetic effects at a November 2005 conference titled "Environmental Epigenomics, Imprinting, and Disease Susceptibility," held in Durham, North Carolina, and sponsored in part by the NIEHS. Some of the strongest, decade-old evidence shows progressive increases in DNA methylation in aging colon tissues, and more recent evidence links hypermethylation with atherosclerosis. Altered, age-related methylation has also been found in tissues in the stomach, esophagus, liver, kidney, and bladder, as well as the tissue types studied by Esteller. Much of Issa's current work focuses on the links between epigenetic processes, aging, the environment, and cancer, and possible ways to therapeutically reverse methylation linked with cancer.

Current and Future Quandaries

The accumulated evidence indicates that many genes, diseases, and environmental substances are part of the epigenetics picture. However, the evidence is still far too thin to form a basis for any overarching theories about which substances and which target genes are most likely to mediate adverse effects of the environment on diseases, says Melanie Ehrlich, a biochemistry professor at the Tulane University School of Medicine and Tulane Cancer Center who has been conducting research on the topic for more than two decades.

That sense of uncertainty generally leaves epigenetics out of the regulatory picture. "It's [too early] to actually use it at the moment," says Julian Preston, acting associate director for health at the EPA's National Health and Environmental Effects Research Laboratory. But Preston says the agency already relies more on its improving understanding of mechanistic processes, including epigenetics, and there is a clear effort within the EPA to expand genomics efforts both within the agency and with others with whom the agency works.

At the FDA, scientists are investigating many drugs that function through epigenetic mechanisms (although as spokes-woman Christine Parker notes, the agency bases its approvals on results of clinical trials, not consideration of the mechanism by which a drug works). One such drug, azacitidine, has been approved for use in the United States to treat myelodysplastic syndrome, a blood disease that can progress to leukemia. The drug turns on genes that had been shut off by methylation. The drug's epigenetic function doesn't make it a "miracle drug," however. Trials indicate it benefits only 15% of those who take it, and a high percentage of people suffer serious side effects, including nausea (71%), anemia (70%), vomiting (54%), and fever (52%).

Ehrlich points out that azacitidine also has effects at the molecular level-such as inhibiting DNA replication and apoptosis-that may be part of its therapeutic benefits. The drug's mixed results might also be explained in part by a study published in the October 2004 issue of Cancer Cell by Andrew Feinberg, director of the Johns Hopkins University Center for Epigenetics in Common Human Disease, and his colleagues. They found that each of two tested drugs, trichostatin A and 5-aza-2′-deoxycytidine (which is related to azacitidine), can turn on hundreds of genes while also turning off hundreds of others. If that finding holds in other studies, it suggests one key reason why it is so difficult to create a drug that doesn't cause unintended side effects.

Public and Private

Despite the potentially huge role that epigenetics may play in human disease, investment in this area of study remains tiny compared to that devoted to traditional genetics work. Several efforts to change that are under way.

In Europe, the Human Epigenome Project was officially launched in 2003 by the Wellcome Trust Sanger Institute, Epigenomics AG, and the Centre National de Génotypage. The group's focus is on DNA methylation research tied to chromosomes 6, 13, 20, and 22. They may be joined soon by organizations in Germany and India, where scientists plan to work on chromosomes 21 and X, respectively, says Sanger senior investigator Stephan Beck.

But comprehensively studying all the epigenetic and epigenomic factors related to a multitude of diseases and health conditions will take much more work. "A [comprehensive] Human Epigenome Project is a lot more complicated than a Human Genome Project," Jones says. "There's only one genome, [but] an epigenome varies in each and every tissue." The Human Genome Project was a worldwide effort that took more than a decade and billions of dollars to complete.

Jones and Robert Martienssen addressed some of the complexities of a comprehensive, worldwide Human Epigenome Project in the 15 December 2005 issue of Cancer Research. Reporting on a June 2005 workshop convened by the American Association for Cancer Research, they concluded that, despite all the looming difficulties, such a project is essential, and the technology is sufficiently advanced to begin.

"I think it's going to happen a lot sooner than I thought just a year or so ago," Jirtle says. A group of researchers has already started the footwork to launch a U.S. complement to the European Human Epigenome Project effort [see box, p. A165].

Other efforts are gaining ground. Another European group, the Epigenome Network of Excellence, took off in June 2004. This information exchange network includes members in the public and private sectors spread throughout ten Western European countries. Their objectives are to coordinate research, provide mentors, and encourage dialogue via their website. And in Asia, a conference held 7-10 November 2005 in Tokyo, "Genome-Wide Epigenetics 2005," was dedicated in large part to facilitating a coordinated epigenomics research effort in Japan and possibly all of Asia, says Ushijima, one of the conference's organizers.

In the United States, the National Cancer Institute and the National Human Genome Research Institute formally kicked off a major effort 13 December 2005 that will include epigenomic work. The pilot project of The Cancer Genome Atlas, funded by $50 million each from the two institutes, is designed to lay the groundwork for comprehensive study of genomic factors related to human cancer. The initial three-year effort is expected to focus on just two or three of the more than 200 cancers known to exist, but if it's successful in developing methods and technologies, the number of cancers evaluated could then expand. If a high number of cancer genes are eventually scrutinized, the effort would be the equivalent of thousands of Human Genome Projects.

To help push the boundaries further, the NIEHS and the National Cancer Institute are in the midst of awarding grants totaling $3.75 million to study a wide range of epigenetic topics, such as identification of high-risk populations, dietary influences on cancer, and detailed study of numerous specific mechanisms linking environmental agents with epigenetic mechanisms and resulting disease. The dozen or so recipients are expected to launch their projects by fall 2006.

The NIEHS has also begun to integrate epigenomics projects into its research portfolio over the past five to six years. "It's an emerging area that's very important," says Frederick Tyson, a program administrator in the NIEHS Division of Extramural Research and Training. And epigenetics is likely to be one of the half dozen or so most important considerations as NIEHS proceeds with its Environmental Genome Project, according to institute director David Schwartz.

The DNA Methylation Society, a professional group, has been growing slowly but steadily over the past decade, says founder and current vice president Ehrlich. As part of its efforts, the society launched a journal, Epigenetics, in January 2006 with the goal of covering a full spectrum of epigenetic considerations-medical, nutritional, psychological, behavioral-in any organism. Such groups are a valuable rallying point for this field, Jirtle says. He himself slowly worked his way into epigenetics from an initial cancer focus, and his segue is typical of many. "If you study epigenetics, you don't have a home; we come from all different fields," he says.

Interest in the private sector is also picking up. For instance, Epigenomics AG, with offices in Berlin and Seattle, is working on early detection and diagnosis of cancer and endometriosis (for which there is limited evidence of an epigenetic component), as well as development of products to predict effectiveness of drugs to treat these diseases. Founded in 1998, and now with about 150 employees, the company is focusing on DNA methylation mechanisms, and is working with companies such as Abbott Laboratories, Johnson & Johnson, Philip Morris, Roche Diagnostics, Pfizer, and AstraZeneca. CEO Oliver Schacht says the surging interest in this field is typified by the difference between the 2004 American Association for Cancer Research conference, which had half a dozen or so talks or posters on epigenetics, and the 2005 event, which had about 200.

Tool Time

If epigenetic work is to continue breaking new ground, many observers say technology will need to continue advancing. Jones and Martienssen note in their paper that there must be additional improvements in high-throughput technologies, analytical techniques, computational capability, mechanistic studies, and bioinformatic strategies. They also say there is a need for basics such as standardized reagents and a consistent supply of antibodies for testing.

Preston agrees with many of these ideas, and says there is also a need to develop a comprehensive tally of all proteins in the cell and to get better protein modification information. He says universities are recognizing the demand for the talents needed to solve epigenomics problems, and are increasing their efforts to cover these topics in various ways, especially at the graduate school level.

Other groups are doing their part by creating tools to further the field. All the imprinted genes identified so far are tracked in complementary efforts by Morison's and Jirtle's groups and the Mammalian Genetics Unit of the U.K. Medical Research Council. The European managers of the DNA Methylation Database have assembled a compendium of known DNA methylations that, although not comprehensive, still provides a useful tool for researchers investigating the roughly 22,000 human genes.

Kunio Shiota, a professor of cellular biochemistry at the University of Tokyo and one of the co-organizers of the November 2005 Tokyo conference, says epigenetic advances will rely in part on a range of processes that are slowly becoming familiar to more researchers-massively parallel signature sequencing (MPSS), chromatin immunoprecipitation microarray analysis (ChIP-chip), DNA adenine methyltransferase identification (Dam-ID), protein binding microarrays (PBM), DNA immunoprecipitation microarray analysis (DIP-chip), and more. Someday, he says, these terms could become fully as familiar as MRI and EKG.

The rapidly growing acceptance of epigenetics, a century after it first surfaced, is a huge step forward, in Jirtle's opinion. "We've done virtually nothing so far," he says. "I'm biased, but the tip of the iceberg is genomics and single-nucleotide polymorphisms. The bottom of the iceberg is epigenetics."

U.S. Human Epigenome Project

In December 2005 a group of 40 international scientists publicly proposed a U.S. Human Epigenome Project to complement a European project of the same name launched in 2003. Group member Andrew Feinberg, a geneticist at the Johns Hopkins University School of Medicine, says, "We're hoping to see how this idea takes hold. There is this ocean of information that is largely unexplored."

The goal of the U.S. project will be to comprehensively map methylation and histone modifications -the two main classes of epigenetic modifications-in a diverse set of normal tissues. These epigenomes would then serve as a reference for comparison with diseased tissues, revealing epigenetic causes of disease. Project organizers are now compiling a detailed proposal, with budget estimates and a timeline.

Although both the U.S. and European projects ultimately aim to map all genes, the U.S. effort will look at different tissue and cell types than the European effort, and will also look at model organisms like yeast and the fly. The two groups are already working closely together in planning their projects to avoid redundancies, and this cooperation will likely continue.

Understanding cancer would be one long-term goal for the U.S. project, but epigenetics-changes in gene expression heritable from cell to daughter cell without changes in DNA sequence-transcends any one disease. "It has profound implications in aging, neurological disorders, and child development," says Peter Jones, another group member and director of the Norris Comprehensive Cancer Center at the University of Southern California. Jones and his colleagues argue that the importance of epigenetics in human disease, together with the maturing of technologies for mapping epigenetic changes, make a human epigenome project both critical and feasible.

Epigenetics, says cancer biologist Jean-Pierre Issa of The University of Texas M.D. Anderson Cancer Center, could prove more important than genetics for understanding environmental causes of disease. "Cancer, atherosclerosis, Alzheimer's disease [are all] acquired diseases where the environment very likely plays an important role," he points out. "And there's much more potential for the epigenome to be affected ... than the genome itself. It's just more fluid and more easy to be the culprit." - Ken Garber

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For nearly a century after the term "epigenetics" first surfaced on the printed page, researchers, physicians, and others poked around in the dark crevices of the gene, trying to untangle the clues that suggested gene function could be altered by more than just changes in sequence.

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The battle between nature and nurture | Irene Gallego Romero | TEDxNTU