Gene-environment Interplay Research Articles

Etiological Contributions to the Covariation Between Children’s Perceptions of Inter-Parental Conflict and Child Behavioral Problems

Prior work has suggested that inter-parental conflict likely plays an etiological role in child behavior problems. However, family-level measurement of inter-parental conflict in most traditional child twin studies has made it difficult to tease apart the specific causal mechanisms underlying this association. The Children's Perception of Inter-parental Conflict scale (CPIC) provides a child-specific measurement tool for examining these questions, as its subscales tap multiple dimensions of conflict assessed from the child's (rather than the parent's) perspective. The current study examined (1) the degree of genetic and environmental influence on each of the CPIC subscales, and (2) etiological contributions to the covariation between the CPIC scales and parental reports of child behavioral problems. The CPIC was completed by 1,200 child twins (aged 6-11 years) from the Michigan State University Twin Registry (MSUTR). Parents completed the Child Behavior Checklist (CBCL) to assess child internalizing and externalizing behavior problems. Multivariate models were examined to evaluate the relative contributions of genetic and environmental factors to both the CPIC scales and to their overlap with child behavioral outcomes. Modeling results indicated no significant moderation of sex or age. Significant environmental overlap emerged between the CPIC conflict properties scale and child internalizing and externalizing problems. By contrast, significant genetic correlations emerged between the CPIC self-blame scale and externalizing problems as well as between the CPIC threat scale and internalizing problems. Overall, findings suggest that the subscales of the CPIC are somewhat etiologically diverse and may provide a useful tool for future investigations of possible gene-environment interplay.

The genetics of addiction-a translational perspective.

Addictions are serious and common psychiatric disorders, and are among the leading contributors to preventable death. This selective review outlines and highlights the need for a multi-method translational approach to genetic studies of these important conditions, including both licit (alcohol, nicotine) and illicit (cannabis, cocaine, opiates) drug addictions and the behavioral addiction of disordered gambling. First, we review existing knowledge from twin studies that indicates both the substantial heritability of substance-specific addictions and the genetic overlap across addiction to different substances. Next, we discuss the limited number of candidate genes which have shown consistent replication, and the implications of emerging genomewide association findings for the genetic architecture of addictions. Finally, we review the utility of extensions to existing methods such as novel phenotyping, including the use of endophenotypes, biomarkers and neuroimaging outcomes; emerging methods for identifying alternative sources of genetic variation and accompanying statistical methodologies to interpret them; the role of gene–environment interplay; and importantly, the potential role of genetic variation in suggesting new alternatives for treatment of addictions.

Primary Prevention of Atherosclerosis

Innovative advances in understanding the pathogenesis of atherosclerosis have been achieved over the past 25 years. Although elevated levels of serum low-density lipoprotein cholesterol (LDL-C) are the major cause of onset of the disease, as established by a large number of superb epidemiological, clinical, and experimental studies, important novel factors have entered the arena of the atherogenic process. Besides the historical oxidative hypothesis that states that oxidized LDL, by escaping the homeostatic mechanism, strongly accelerates plaque formation, more recent evidence has given credit to vascular inflammation and apoptosis as crucial players in the progression of atherosclerosis.1–3 The disease has also been linked to the subintimal infiltration of immune cells and endothelial dysfunction induced by cardiovascular risk factors. Currently, endothelial dysfunction is considered one of the first stages of vascular damage and an early event in atherogenesis.1–3 Etiologic and pathogenetic factors, of both genetic and environmental origin, act together to promote local and systemic effects that lead to the onset, progression, and final outcome of the atherosclerotic disease. The clinical sequelae of atherosclerosis, myocardial infarction, stroke, and peripheral arterial disease depend on the affected vascular district, which in turn depends on complex gene-environment interplay. Despite the sudden occurrence of clinical symptoms, however, the evolution of atherosclerosis is very slow, which provides an opportunity for early diagnosis. In fact, a breakthrough in the field has been to recognize that although atherosclerosis generates severe diseases that most frequently affect middle-aged to old people, atherogenesis begins very early in life, even at the fetal stage.4,5 Primary prevention of any disease is more effective if started sooner. Therefore, it is of paramount importance to identify high-risk individuals and to initiate primary prevention in a timely manner, especially for atherosclerosis, which can begin its slow but relentless …

Developmental Trajectory and Environmental Moderation of the Effect of ALDH2 Polymorphism on Alcohol Use

In the aldehyde dehydrogenase 2 (ALDH2) gene, the ALDH2*2 allele, prevalent in East Asian populations, encodes an enzyme with severely reduced activity, thereby disrupting the normal metabolism of alcohol. Possession of the ALDH2*2 allele has been repeatedly shown to be associated with lower risk for alcohol dependence and reduced alcohol use. However, relatively few studies have considered whether the magnitude of the effect of ALDH2 polymorphism upon drinking is related to developmental stage or varies by environmental context. In a longitudinally assessed sample of 356 adopted adolescents and young adults of East Asian descent, we examined the progression over time of the relationship between ALDH2 genotype and multiple measures of drinking behavior. We also sought to determine whether the environmental influences of nonbiological parent and elder sibling alcohol use and misuse, as well as deviant peer behavior, moderated the effect of ALDH2 genotype upon alcohol use. Across all measures of alcohol use, the association between ALDH2*2 allele possession and reduced drinking went from negligible to moderate between mid-adolescence and early adulthood. A combined index of adoptive parent alcohol use and misuse consistently moderated the protective effect of the ALDH2*2 allele across the measures of quantity and frequency of alcohol use, and symptomology, such that high parental alcohol use and misuse reduced the protective effect of the ALDH2*2 allele, while low parental alcohol use and misuse enhanced the effect of the allele. Neither a combined index of elder sibling alcohol use and misuse, nor deviant peer behavior was consistently related to the effect of ALDH2 genotype. The protective effect of the ALDH2*2 allele increases over the course of adolescence and young adulthood and is modified by the environmental influence of parental alcohol use and misuse. As such, ALDH2 provides a model system for exploring the nature of gene-environment interplay across development.

Genetics and Peer Relations: A Review

Researchers have become increasingly interested in uncovering how genetic factors work together with the peer environment in influencing development. This article offers an overview of the state of knowledge. It first describes the different types of gene‐environment correlations (rGE) and gene‐environment interactions (GxE) that are of relevance for understanding the role of peer relations as well as the two main methodologies of genetically informed research, that is, the quantitative genetic approach and molecular genetics. This is followed by an overview of recent studies that examined different mechanisms of gene‐environment interplay involving peer relations in childhood and adolescence. The article concludes with an outline of future directions in genetically informed peer relations research as well as the implications for theory and practice.

The developmental origins of externalizing behavioral problems: Parental disengagement and the role of gene–environment interplay

A line of research has revealed that the influence of genes on behavioral development is closely tied to environmental experiences. Known as gene–environment interaction, research in this area is beginning to reveal that variation in parenting behaviors may moderate genetic influences on antisocial behaviors in children. Despite growing interest in gene–environment interaction research, little evidence exists concerning the role of maternal disengagement in the conditioning of genetic influences on childhood behavioral problems. The current study is intended to address this gap in the literature by analyzing a sample of twin pairs drawn from the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B). Analysis of the ECLS-B provided evidence that maternal disengagement moderates genetic influences on the development of externalizing problems.

Gene-environment interplay in the association between pubertal timing and delinquency in adolescent girls.

Early pubertal timing places girls at elevated risk for a breadth of negative outcomes, including involvement in delinquent behavior. While previous developmental research has emphasized the unique social challenges faced by early maturing girls, this relation is complicated by genetic influences for both delinquent behavior and pubertal timing, which are seldom controlled for in existing research. The current study uses genetically informed data on 924 female-female twin and sibling pairs drawn from the National Longitudinal Study of Adolescent Health to (1) disentangle biological versus environmental mechanisms for the effects of early pubertal timing and (2) test for gene-environment interactions. Results indicate that early pubertal timing influences girls' delinquency through a complex interplay between biological risk and environmental experiences. Genes related to earlier age at menarche and higher perceived development significantly predict increased involvement in both nonviolent and violent delinquency. Moreover, after accounting for this genetic association between pubertal timing and delinquency, the impact of nonshared environmental influences on delinquency are significantly moderated by pubertal timing, such that the nonshared environment is most important among early maturing girls. This interaction effect is particularly evident for nonviolent delinquency. Overall, results suggest early maturing girls are vulnerable to an interaction between genetic and environmental risks for delinquent behavior.

Gene–Environment Interaction in Major Depression and Antidepressant Treatment Response

Response to antidepressants is interindividually variable. It has been suggested that this variability is a direct consequence of etiological heterogeneity. Therefore, the same genes, environments, and gene-environment interactions implicated in different etiological pathways to depression may also predict response to treatment. This article reviews the evidence relevant to this hypothesis by first outlining the roles of genes, environments, and gene-environment interplay in the etiology of depression, and then considering the same factors in treatment response. Environmental exposures, such as childhood maltreatment, are potent predictors of both depression and treatment response. Although alone genetic factors have failed to consistently predict either phenotype, several polymorphisms have been shown to moderate the effects of environmental adversity on the development of depression and treatment response. These findings suggest that the dissection of etiological pathways to depression may provide the key to understanding and predicting response to antidepressants.

A new public health genomics model for common complex diseases, with an application to common behavioral disorders.

In the light of common forms of gene-environment interplay, particularly epigenomics and ecogenetics, the incorporation of envirome data into public health genomics models becomes necessary. Developing and restructuring public health genomics models is essential within the context of common complex diseases. We developed a novel theoretical model integrating a gene-environment interaction paradigm into public health genomics, which integrates four main sources of data: personal genome data, personal envirome data, molecular genetic/genomic evidence and environmental factors implicated in gene-environment interactions underlying common complex disease phenotypes. Collectively, this knowledge is fed into public health policy development. This model is the first public health genomics model that incorporates gene-environment interactions within the context of common complex disorders, and is applied to behavioral conditions. Our model proposes, for the first time, an understanding of behavioral disorders from the genomic perspective, combining it with known environmental factors within the framework of public health. Application of this model will enable evidence-based behavioral interventions at the public health level and facilitate genome-based public health policy development for behavioral conditions.

Stressful life events and the serotonin transporter gene ( 5-HTT ) in recurrent clinical depression

An interaction between recent stressful life events (SLEs) and a serotonin transporter promoter polymorphism (5-HTTLPR) in depression has been inconsistently reported. Some of this variability may be due to a previous focus on sub-clinical depression, inclusion of individuals at the lower or upper ends of the age-span, or assumptions concerning the degree of dominance of the low expressing allele. Therefore, a large sample of patients with recurrent clinically diagnosed depression and controls screened for absence of depression was utilised to examine the moderating effect of each 5-HTTLPR genetic model on the association between SLEs and severe depressive episodes. A sample of 1236 recurrent unipolar depression cases and 598 age-matched, never psychiatrically ill controls completed the List of Threatening Experiences Questionnaire to assess the number of SLEs experienced in the 6 months prior to the most severe depressive episode (cases) or interview (controls). DNA extracted from blood or cheek swabs was genotyped for the short (s) and long (l) alleles of 5-HTTLPR. A greater number of SLEs were reported by cases than controls and this held across all genotypic groups. There was no main effect of 5-HTTLPR on depression and no evidence of interaction between total SLEs and any of the 5-HTTLPR genetic models. The results were the same for men and women. Utilisation of retrospective self-reported SLEs may have reduced the accuracy of the findings and the cross-sectional design prevents causal inference. This study failed to find evidence of gene-environment interplay in recurrent clinical depression.

Editorial: Focusing on a moving target: key themes for research and practice in adolescent mental health

Editorial: Focusing on a moving target: key themes for research and practice in adolescent mental health

Physical punishment and childhood aggression: the role of gender and gene–environment interplay

A large body of research has linked spanking with a range of adverse outcomes in children, including aggression, psychopathology, and criminal involvement. Despite evidence concerning the association of spanking with antisocial behavior, not all children who are spanked develop antisocial traits. Given the heterogeneous effects of spanking on behavior, it is possible that a third variable may condition the influence of corporal punishment on child development. We test this possibility using data drawn from a nationally representative dataset of twin siblings. Our findings suggest that genetic risk factors condition the effects of spanking on antisocial behavior. Moreover, our results provide evidence that the interaction between genetic risk factors and corporal punishment may be particularly salient for males.

Gene-Environment Interplay, Family Relationships, and Child Adjustment

This paper reviews behavioral genetic research from the past decade that has moved beyond simply studying the independent influences of genes and environments. The studies considered in this review have instead focused on understanding gene - environment interplay, including genotype - environment correlation ( rGE) and genotype × environment interaction (G × E). Studies have suggested that rGE is an important pathway through which family relationships are associated with child adjustment. Also important are direct causal influences of family relationships on child adjustment, independent of genetic confounds. Other studies have indicated that genetic and environmental influences on child adjustment are moderated by different levels of family relationships in G × E interactions. Genetically informed studies that have examined family relations have been critical to advancing our understanding of gene - environment interplay.

Biopsychosocial Models and the Study of Family Processes and Child Adjustment

Biopsychosocial Models and the Study of Family Processes and Child Adjustment

Heritability in the Era of Molecular Genetics: Some Thoughts for Understanding Genetic Influences on Behavioural Traits

Genetic influences on behavioural traits are ubiquitous. When behaviourism was the dominant paradigm in psychology, demonstrations of heritability of behavioural and psychological constructs provided important evidence of its limitations. Now that genetic influences on behavioural traits are generally accepted, we need to recognise the limitations of heritability as an indicator of both the aetiology and likelihood of discovering molecular genetic associations with behavioural traits. We review those limitations and conclude that quantitative genetics and genetically informative research designs are still critical to understanding the roles of gene–environment interplay in developmental processes, though not necessarily in the ways commonly discussed. Copyright © 2011 John Wiley & Sons, Ltd.

Some Key Issues in the Study of Gene–Environment Interplay: Activation, Deactivation, and the Role of Development

Gene–environment interaction (GxE) is thought to constitute a fundamental mechanism though which genes influence human behavior. In the excitement about GxE, however, the deliberative approach that typically characterizes empirical social science research has been inconsistently applied. The current review highlights areas where more work is needed. First, although most GxE research to date has focused on the augmentation of genetic influences by extreme environmental pathogens, normal-range environmental risk factors may also act via GxE. Second, environmental risk and protective factors may serve to “deactivate”, rather than augment, genetic influences. Finally, few GxE studies have meaningfully considered the role of development.

Psychobiological processes: A gene–environment transactional hypothesis

More and more concern over gene–environment interplay has been emerging recently. However studies covering this field of interest mainly focus on environmental toxicants. In this hypothesis I briefly review some outcomes of this area of interest related to social and physical environment, and try and elucidate a psychobiological pathway that could explain some of the mechanisms underlying this interplay. A gene–environment transactional approach related to neurobiological processes is proposed in this perspective.

Animal Models of Human Anxiety Disorders: Reappraisal From a Developmental Psychopathology Vantage Point

We are witnessing a tremendous expansion of strategies and techniques that derive from basic and preclinical science to study the fine genetic, epigenetic, and proteomic regulation of behavior in the laboratory animal. In this endeavor, animal models of psychiatric illness are becoming the almost exclusive domain of basic researchers, with lesser involvement of clinician researchers in their conceptual design, and transfer into practice of new paradigms. From the side of human behavioral research, the growing interest in gene-environment interplay and the fostering of valid endophenotypes are among the few substantial innovations in the effort of linking common mental disorders to cutting-edge clinical research questions. We argue that it is time for cross-fertilization between these camps. In this article, we a) observe that the "translational divide" can-and should-be crossed by having investigators from both the basic and the clinical sides cowork on simpler, valid "endophenotypes" of neurodevelopmental relevance; b) emphasize the importance of unambiguous physiological readouts, more than behavioral equivalents of human symptoms/syndromes, for animal research; c) indicate and discuss how this could be fostered and implemented in a developmental framework of reference for some common anxiety disorders and ultimately lead to better animal models of human mental disorders.

Catechol‐O‐methyltransferase Val158Met genotype, parenting practices and adolescent alcohol use: testing the differential susceptibility hypothesis

Recently, first evidence has been reported for a gene-parenting interaction (G × E) with regard to adolescent alcohol use. The present investigation set out to extend this research using the catechol-O-methyltransferase (COMT) Val(158) Met polymorphism as a genetic susceptibility factor. Moreover, the current study examined whether a potential G×E would be consistent with one of two models of gene-environment interplay (genetic vulnerability vs. differential susceptibility). Data were collected as part of an ongoing epidemiological cohort study following the outcome of early risk factors from birth into adulthood. Two hundred and eighty-five participants (130 males, 155 females) were genotyped for the COMT Val(158) Met polymorphism and were administered an alcohol interview, providing measures of current frequency and amount of drinking at ages 15 and 19 years. Information on three dimensions of perceived parenting behavior was obtained from the 15-year-olds. Adolescents homozygous for the Met allele showed higher drinking activity at age 19 years when their parents had engaged in less supervision or were less involved, while their drinking activity was reduced under conditions of favorable parenting. No such relationship was found in individuals carrying the Val allele. The present findings correspond with the pattern of results predicted by the differential susceptibility hypothesis, suggesting that environmental variation would have a greater impact in individuals carrying a genetic susceptibility such that, in this group, exposure to negative environmental conditions would result in more adverse outcomes and the experience of favorable conditions would lead to more positive outcomes.

Editorial: Gene-environment interplay and development

Editorial: Gene-environment interplay and development