Gene-environment correlation
Encyclopedia
Gene-environment correlation (or genotype-environment correlation) is said to occur when exposure to environmental conditions depends on an individual's genotype
.
Gene-environment correlation can also arise from non-causal mechanisms, including evolutionary processes and behavioral 'contamination' of the environmental measure. Evolutionary processes, such as genetic drift
and natural selection
, can cause allele frequencies to differ between populations. For example, exposure to malaria-bearing mosquitoes over many generations may have caused the higher allele frequency among certain ethnic groups for the sickle hemoglobin
(HbS) allele, a recessive mutation that causes sickle-cell disease
but confers resistance against malaria
. In this way, HbS genotype has become associated with the malarial environment.
Environments are heritable because genotype influences the behaviours that evoke, select, and modify features of the environment. Thus, environments less amenable to behavioural modification tend to be less heritable. For example, negative life events that are beyond the control of the individual (e.g., the death of a loved one, losing one’s home in a natural disaster) have lower heritability than negative life events that may be dependent on an individual’s behaviour (e.g., getting a divorce, getting fired from a job). Similarly, personal life events (i.e., events that occur directly to an individual) are more highly heritable than network life events (i.e., events that occur to someone within an individual’s social network, thus affecting the individual indirectly).
investigations. The Collaborative Studies on Genetics of Alcoholism
(COGA) group has reported that a single-nucleotide polymorphism in intron 7 of the gamma-aminobutyric acid A a2 receptor (rs279871; GABRA2) was associated with alcohol dependence and marital status. Individuals who had the high-risk GABRA2 variant (i.e., the variant associated with alcohol dependence) were less likely to be married, in part because they were at higher risk for antisocial personality disorder
and were less likely to be motivated by a desire to please others. There is also molecular evidence for passive gene-environment correlation. A recent study found that children were almost 2.5 times more likely to be diagnosed with attention-deficit hyperactivity disorder
(ADHD) if their mothers were divorced, separated, or never married. In this sample, however, mothers possessing the short allele of the dopamine receptor
gene DRD2 were more likely to be divorced, separated, or never married. Moreover, their children were more likely to have ADHD. Therefore, part of the association between parental marital status and ADHD diagnosis among children in this sample is due to the confounding variable of maternal DRD2 genotype. Both of these studies also found evidence for gene-environment interaction
.
by genotype. That is, the relationship may be spurious
(not causal) because the same genetic factors influence both exposure to environmental risk and disease. If so then reducing environmental exposure will not reduce the risk for disease.
For example, a study of children born to twin sisters investigated whether the relationship between parental divorce and offspring alcohol and emotion
al problems was causal or confounded by parental genotype. The study found that the offspring of twin sisters who were discordant for divorce had equally high levels of emotional problems, suggesting that genetic factors which made twin siblings divorce-prone also increased their children’s risk for depression and anxiety. This finding suggests that preventing the parents’ divorce would have had little impact on offspring risk for emotional problems (although the findings for alcohol problems were consistent with a causal role for divorce).
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
.
Definition
Gene-environment correlations can arise by both causal and non-causal mechanisms. Of principal interest are those causal mechanisms, which indicate genetic control over environmental exposure. Genetic variants influence environmental exposure indirectly via behavior. Three causal mechanisms giving rise to gene-environment correlations have been described.- (i) Passive gene-environment correlation refers to the association between the genotype a child inherits from her parents and the environment in which the child is raised. Parents create a home environment that is influenced by their own heritableHeritabilityThe Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...
characteristics. Biological parents also pass on genetic material to their children. When the children's genotype also influences their behavioral or cognitive outcomes, the result can be a spurious relationshipSpurious relationshipIn statistics, a spurious relationship is a mathematical relationship in which two events or variables have no direct causal connection, yet it may be wrongly inferred that they do, due to either coincidence or the presence of a certain third, unseen factor In statistics, a spurious relationship...
between environment and outcome. For example, because parents who have histories of antisocial behavior (which is moderately heritable) are at elevated risk of abusing their children, a case can be made for saying that maltreatment may be a marker for genetic risk that parents transmit to children rather than a causal risk factor for children’s conduct problems.
- (ii) Evocative (or reactive) gene-environment correlation happens when an individual's (heritable) behavior evokes an environmental response. For example, the association between marital conflict and depression may reflect the tensions that arise when engaging with a depressed spouse rather than a causal effect of marital conflict on risk for depression.
- (iii) Active gene-environment correlation occurs when an individual possesses a heritable propensity to select environmental exposure. For example, individuals who are characteristically extroverted may seek out very different social environments than those who are shy and withdrawn.
Gene-environment correlation can also arise from non-causal mechanisms, including evolutionary processes and behavioral 'contamination' of the environmental measure. Evolutionary processes, such as genetic drift
Genetic drift
Genetic drift or allelic drift is the change in the frequency of a gene variant in a population due to random sampling.The alleles in the offspring are a sample of those in the parents, and chance has a role in determining whether a given individual survives and reproduces...
and natural selection
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....
, can cause allele frequencies to differ between populations. For example, exposure to malaria-bearing mosquitoes over many generations may have caused the higher allele frequency among certain ethnic groups for the sickle hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
(HbS) allele, a recessive mutation that causes sickle-cell disease
Sickle-cell disease
Sickle-cell disease , or sickle-cell anaemia or drepanocytosis, is an autosomal recessive genetic blood disorder with overdominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various...
but confers resistance against malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
. In this way, HbS genotype has become associated with the malarial environment.
Quantitative genetic studies
Twin and adoption studies have provided much of the evidence for gene-environment correlations by demonstrating that putative environmental measures are heritable. For example, studies of adult twins have shown that desirable and undesirable life events are moderately heritable as are specific life events and life circumstances, including divorce, the propensity to marry, marital quality and social support. Studies in which researchers have measured child-specific aspects of the environment have also shown that putative environmental factors, such as parental discipline or warmth, are moderately heritable. Television viewing, peer group orientations and social attitudes have all been shown to be moderately heritable. There is also a growing literature on the genetic factors influencing behaviors that constitute a risk to health, such as the consumption of alcohol, tobacco and illegal drugs, and risk-taking behaviors. Like parental discipline, these health related behaviors are genetically influenced, but are thought to have environmentally mediated effects on disease. To the extent that researchers have attempted to determine why genes and environments are correlated, most evidence has pointed to the intervening effects of personality and behavioral characteristics.Environments are heritable because genotype influences the behaviours that evoke, select, and modify features of the environment. Thus, environments less amenable to behavioural modification tend to be less heritable. For example, negative life events that are beyond the control of the individual (e.g., the death of a loved one, losing one’s home in a natural disaster) have lower heritability than negative life events that may be dependent on an individual’s behaviour (e.g., getting a divorce, getting fired from a job). Similarly, personal life events (i.e., events that occur directly to an individual) are more highly heritable than network life events (i.e., events that occur to someone within an individual’s social network, thus affecting the individual indirectly).
Molecular genetic studies
Evidence for the existence of gene-environment correlations has recently started to accrue from molecular geneticMolecular genetics
Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...
investigations. The Collaborative Studies on Genetics of Alcoholism
Collaborative Studies on Genetics of Alcoholism
The Collaborative Studies on the Genetics of Alcoholism is a nine-center research project in the United States designed to examine the genetics involved in alcoholism...
(COGA) group has reported that a single-nucleotide polymorphism in intron 7 of the gamma-aminobutyric acid A a2 receptor (rs279871; GABRA2) was associated with alcohol dependence and marital status. Individuals who had the high-risk GABRA2 variant (i.e., the variant associated with alcohol dependence) were less likely to be married, in part because they were at higher risk for antisocial personality disorder
Antisocial personality disorder
Antisocial personality disorder is described by the American Psychiatric Association's Diagnostic and Statistical Manual, fourth edition , as an Axis II personality disorder characterized by "...a pervasive pattern of disregard for, and violation of, the rights of others that begins in childhood...
and were less likely to be motivated by a desire to please others. There is also molecular evidence for passive gene-environment correlation. A recent study found that children were almost 2.5 times more likely to be diagnosed with attention-deficit hyperactivity disorder
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
(ADHD) if their mothers were divorced, separated, or never married. In this sample, however, mothers possessing the short allele of the dopamine receptor
Dopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
gene DRD2 were more likely to be divorced, separated, or never married. Moreover, their children were more likely to have ADHD. Therefore, part of the association between parental marital status and ADHD diagnosis among children in this sample is due to the confounding variable of maternal DRD2 genotype. Both of these studies also found evidence for gene-environment interaction
Gene-environment interaction
Gene–environment interaction is the phenotypic effect of interactions between genes and the environment....
.
Significance
Doctors want to know whether exposure to environmental risk causes disease. The fact that environmental exposures are heritable means that the relationship between environmental exposure and disease may be confoundedConfounding
In statistics, a confounding variable is an extraneous variable in a statistical model that correlates with both the dependent variable and the independent variable...
by genotype. That is, the relationship may be spurious
Spurious relationship
In statistics, a spurious relationship is a mathematical relationship in which two events or variables have no direct causal connection, yet it may be wrongly inferred that they do, due to either coincidence or the presence of a certain third, unseen factor In statistics, a spurious relationship...
(not causal) because the same genetic factors influence both exposure to environmental risk and disease. If so then reducing environmental exposure will not reduce the risk for disease.
For example, a study of children born to twin sisters investigated whether the relationship between parental divorce and offspring alcohol and emotion
Emotion
Emotion is a complex psychophysiological experience of an individual's state of mind as interacting with biochemical and environmental influences. In humans, emotion fundamentally involves "physiological arousal, expressive behaviors, and conscious experience." Emotion is associated with mood,...
al problems was causal or confounded by parental genotype. The study found that the offspring of twin sisters who were discordant for divorce had equally high levels of emotional problems, suggesting that genetic factors which made twin siblings divorce-prone also increased their children’s risk for depression and anxiety. This finding suggests that preventing the parents’ divorce would have had little impact on offspring risk for emotional problems (although the findings for alcohol problems were consistent with a causal role for divorce).
See also
- Nature versus nurtureNature versus nurtureThe nature versus nurture debate concerns the relative importance of an individual's innate qualities versus personal experiences The nature versus nurture debate concerns the relative importance of an individual's innate qualities ("nature," i.e. nativism, or innatism) versus personal experiences...
- Gene-environment interactionGene-environment interactionGene–environment interaction is the phenotypic effect of interactions between genes and the environment....
- Genetic predispositionGenetic predispositionA genetic predisposition is a genetic affectation which influences the phenotype of an individual organism within a species or population but by definition that phenotype can also be modified by the environmental conditions. In the rest of the population, conditions cannot have that effect...
- Psychiatric geneticsPsychiatric geneticsPsychiatric genetics, a subfield of behavioral neurogenetics, studies the role of genetics in psychological conditions such as alcoholism, schizophrenia, bipolar disorder, and autism. The basic principle behind psychiatric genetics is that genetic polymorphisms, as indicated by linkage to e.g...