Gene-environment Interplay Research Articles

Identification of a SGCD × Discrimination Interaction Effect on Systolic Blood Pressure in African American Adults in the Jackson Heart Study.

In the United States, hypertension disproportionately afflicts over half of African American adults, many of whom also experience racial discrimination. Understanding gene × discrimination effects may help explain racial disparities in hypertension. We tested for the main effects and interactive effects of 5 candidate single nucleotide polymorphisms (SNPs: rs2116737, rs11190458, rs2445762, rs2597955, and rs2416545) and experiences of discrimination on blood pressure (BP) in African Americans not taking antihypertensive medications in the Jackson Heart Study from Mississippi (n = 2,933). Multiple linear regression models assumed an additive genetic model and adjusted for ancestry, age, sex, body mass index, education, and relatedness. We additionally tested recessive and dominant genetic models. Discrimination was significantly associated with higher diastolic BP (P = 0.003). In contrast, there were no main effects of any SNP on BP. When analyzing SNPs and discrimination together, SGCD (Sarcoglycan Delta; rs2116737) demonstrated a gene × environment interaction. Specifically, an SGCD × Discrimination interaction was associated with systolic BP (β =1.95, P = 0.00028) in a recessive model. Participants carrying a T allele, regardless of discrimination experiences, and participants with a GG genotype and high experiences of discrimination had higher systolic BP than participants with a GG genotype and low experiences of discrimination. This finding suggests the SGCD GG genotype may have a protective effect on systolic BP, but only in a setting of low discrimination. The inclusion of culturally relevant stressors, like discrimination, may be important to understand the gene-environment interplay likely underlying complex diseases with racial health inequities.

Gene-Environment Interplay Linking Peer Victimization With Adolescents’ Trajectories of Depressive Symptoms

ObjectiveThis study examined to what extent genetic and environmental factors explain—either additively or interactively with peer victimization—different trajectories of adolescents’ depressive symptoms and whether genetic factors related to distinct trajectories are correlated with peer victimization. MethodParticipants included 902 twins (52% girls) who self-reported peer victimization and depressive symptoms in grades 6, 7, 8, 9, and 11. ResultsGrowth mixture modeling revealed 3 trajectories of depressive symptoms: low (69.2% of participants), increasing (19.5%), and high-decreasing-increasing (11.3%). Biometric modeling showed that, for both sexes, genetic factors explained roughly half (52.6%, 47.5%) of the probability of following either a low or an increasing trajectory. Genetic influences (41%) were also observed for the high-decreasing-increasing trajectory, albeit only for girls. Nonshared environmental influences explained the remaining variances, along with shared environmental influences (27%) on the high-decreasing-increasing trajectory. Only for the low and the increasing trajectories, nonshared environmental influences increased with more frequent peer victimization (blow = 0.206, 95% CI [0.094, 0.325]; bincreasing = 0.246, 95% CI [0.143, 0.356]). Moreover, peer victimization was associated with a lower probability of a low trajectory and a higher probability of an increasing or high-decreasing-increasing trajectory, and these associations were mostly explained by common underlying genetic factors. ConclusionYouth expressing (partly inherited) depressive symptoms may be at risk of peer victimization. However, increasing depressive symptoms in victims may be mitigated by other environmental factors except for those who enter adolescence with already high levels of depressive symptoms.

Gene-environment interplay in externalizing behavior from childhood through adulthood.

Genetic and environmental influences on externalizing problems are often studied separately. Here, we extended prior work by investigating the implications of gene-environment interplay in childhood for early adult externalizing behavior. Genetic nurture would be indicated if parents' genetic predisposition for externalizing behavior operates through the family environment in predicting offspring early adult externalizing behavior. Evocative gene-environment correlation would be indicated if offspring genetic predisposition for externalizing behavior operates through child externalizing behavior in affecting the family environment and later early adult externalizing behavior. Longitudinal data from seven waves of the TRacking Adolescents' Individual Lives Survey, a prospective cohort study of Dutch adolescents followed from age 11 to age 29 (n at baseline = 2,734) were used. Child externalizing behavior was assessed using self and parent reports. Family dysfunction was assessed by parents. Early adult externalizing behavior was assessed using self-reports. Genome-wide polygenic scores for externalizing problems were constructed for mothers, fathers, and offspring. Offspring polygenic score and child behavior each predicted early adult externalizing problems, as did family dysfunction to a small extent. Parents' polygenic scores were not associated with offspring's early adult externalizing behavior. Indirect effect tests indicated that offspring polygenic score was associated with greater family dysfunction via child externalizing behavior (evocative gene-environment correlation) but the effect was just significant and the effect size was very small. Parents' polygenic scores did not predict family dysfunction, thus the data do not provide support for genetic nurture. A very small evocative gene-environment correlation was detected but effect sizes were much more pronounced for stability in externalizing behavior from childhood through early adulthood, which highlights the necessity to intervene early to prevent later problems.

Racial/ethnic discrimination, ADH1B*3, and coping-motivated drinking among Black college students.

Discrimination due to race and/or ethnicity can be a pervasive stressor for Black college students in the United States beyond general negative life events and has demonstrated associations with adverse health and alcohol outcomes. Genetics may confer individual differences in the risk of drinking to cope with discrimination-related stress. This study tested whether associations of racial/ethnic discrimination with coping drinking motives and alcohol use differ as a function of a well-documented variant in the alcohol dehydrogenase 1B gene (ADH1B*3). Cross-sectional data were obtained from 241 Black students (Mage = 20.04 [range = 18-53]; 66% female) attending a predominantly White university in the northeastern United States. Participants provided a saliva sample for genotyping and self-reported on their racial/ethnic discrimination experiences, coping drinking motives, and past-month total alcohol quantity. Path models demonstrated that associations of discrimination with alcohol quantity directly or indirectly through coping drinking motives did not differ as a function of ADH1B*3, after controlling for gender, age, negative life events, and potential confounding interactions of covariates with model predictors. Regardless of ADH1B*3, greater experience of negative life events was associated with higher coping drinking motives, which in turn were associated with greater alcohol quantity. CONCLUSIONAND SCIENTIFIC SIGNIFICANCE: Findings represent a novel investigation into gene-environment interplay in associations of alcohol use with racial/ethnic discrimination. Findings demonstrate coping-motivated drinking associated with negative life events within Black college drinkers regardless of ADH1B*3. Future research should leverage longitudinal designs to characterize associations of genetics, stressful experiences, and coping-motivated drinking over time.

Polygenic Scores for Plasticity: A New Tool for Studying Gene-Environment Interplay.

Fertility, health, education, and other outcomes of interest to demographers are the product of an individual's genetic makeup and their social environment. Yet, gene × environment (G×E) research deploys a limited toolkit on the genetic side to study the gene-environment interplay, relying on polygenic scores (PGSs) that reflect the influence of genetics on levels of an outcome. In this article, we develop a genetic summary measure better suited for G×E research: variance polygenic scores (vPGSs), which are PGSs that reflect genetic contributions to plasticity in outcomes. First, we use the UK Biobank (N ∼ 408,000 in the analytic sample) and the Health and Retirement Study (N ∼ 5,700 in the analytic sample) to compare four approaches to constructing PGSs for plasticity. The results show that widely used methods for discovering which genetic variants affect outcome variability fail to serve as distinctive new tools for G×E. Second, using the PGSs that do capture distinctive genetic contributions to plasticity, we analyze heterogeneous effects of a UK education reform on health and educational attainment. The results show the properties of a useful new tool for population scientists studying the interplay of nature and nurture and for population-based studies that are releasing PGSs to applied researchers.

Gene and environment interplay in regulating immunotoxicity of different allergens

Allergens can elicit immunotoxic effects in humans. It is often life-threatening and severe that influences the prevalence and course of allergic diseases like asthma, allergic rhinitis, atopic dermatitis, and contact dermatitis. Genetic as well as environmental factors may contribute to allergy and related physiological responses. The pathogenesis of asthma and allergy involves the interaction of genetic markers and environmental factors. Various toxic compounds like metals, foods, even certain kinds of drugs can elicit immunotoxicity. Asthma is subjected to inflammation of the airways; of which genes and environment both are responsible in an interactive way. The innate immunity genes particularly CD 14 and Toll like receptors TLR4 and TLR 2 play an important role on susceptibility to asthma and allergy. The genes interrelated to asthma have been found through Single Nucleotide Polymorphism (SNP) studies. There are other risk factors associated with allergic diseases which require long-term, effective therapeutic approaches as a treatment regimen. The present study is an attempt to highlight the immunological reactions of certain compounds and gene-environment interplay in developing the pathological symptoms associated with asthma.

Regulation of oxytocin receptor gene expression in obsessive\u2013compulsive disorder: a possible role for the microbiota-host epigenetic axis

BackgroundObsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats.ResultsHigher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure.ConclusionsThis is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies.

Maternal depressive symptoms and children's cognitive school readiness: the role of gene-environment interplay.

Maternal depressive symptoms are a robust risk factor for poor cognitive outcomes in children, yet the role of gene-environment interplay in this association is not well understood. The objective of this study was to evaluate gene-environment interaction in the association between maternal depressive symptoms and children's cognitive school readiness. Data come from a population-based birth cohort of 538 twin pairs. Maternal depressive symptoms were self-reported (Centre for Epidemiologic Studies Depression Scale) when children were aged 6 and 18 months (a mean score was used). Children's cognitive school readiness was assessed using the Lollipop Test when children were aged 5 years. Analyses were conducted with structural equation modeling. Maternal depressive symptoms were correlated with children's cognitive school readiness (r = -0.10). Shared environmental factors explained most of the variance in children's cognitive school readiness (52%). The remaining variance was accounted for by genetic (30%) and nonshared environmental factors (18%). As the level of maternal depressive symptoms increased, the relative contribution of nonshared environmental factors to the variance in children's cognitive school readiness increased (0.14 [95% CI: 0.04 to 0.24]), whereas the relative contribution of genetic factors decreased (-0.28 [-0.64 to 0.08]). In contexts of elevated maternal depressive symptoms, environmental - and potentially modifiable - factors may be especially important for shaping children's cognitive outcomes. This suggests that interventions to improve the early childhood environment of children exposed to maternal depressive symptoms may improve their cognitive outcomes.

Mother-child similarity in brain morphology: A comparison of structural characteristics of the brain’s reading network

BackgroundSubstantial evidence acknowledges the complex gene-environment interplay impacting brain development and learning. Intergenerational neuroimaging allows the assessment of familial transfer effects on brain structure, function and behavior by investigating neural similarity in caregiver-child dyads. MethodsNeural similarity in the human reading network was assessed through well-used measures of brain structure (i.e., surface area (SA), gyrification (lG), sulcal morphology, gray matter volume (GMV) and cortical thickness (CT)) in 69 mother-child dyads (children’s age~11 y). Regions of interest for the reading network included left-hemispheric inferior frontal gyrus, inferior parietal lobe and fusiform gyrus. Mother-child similarity was quantified by correlation coefficients and familial specificity was tested by comparison to random adult-child dyads. Sulcal morphology analyses focused on occipitotemporal sulcus interruptions and similarity was assessed by chi-square goodness of fit. ResultsSignificant structural brain similarity was observed for mother-child dyads in the reading network for lG, SA and GMV (r = 0.349/0.534/0.542, respectively), but not CT. Sulcal morphology associations were non-significant. Structural brain similarity in lG, SA and GMV were specific to mother-child pairs. Furthermore, structural brain similarity for SA and GMV was higher compared to CT. ConclusionIntergenerational neuroimaging techniques promise to enhance our knowledge of familial transfer effects on brain development and disorders.

Financial strain moderates genetic influences on self-rated health: support for diathesis–stress model of gene–environment interplay

ABSTRACT Data from the Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium were used to examine predictions of different models of gene-by-environment interaction to understand how genetic variance in self-rated health (SRH) varies at different levels of financial strain. A total of 11,359 individuals from 10 twin studies in Australia, Sweden, and the United States contributed relevant data, including 2,074 monozygotic and 2,623 dizygotic twin pairs. Age ranged from 22 to 98 years, with a mean age of 61.05 (SD = 13.24). A factor model was used to create a harmonized measure of financial strain across studies and items. Twin analyses of genetic and environmental variance for SRH incorporating age, age2, sex, and financial strain moderators indicated significant financial strain moderation of genetic influences on self-rated health. Moderation results did not differ across sex or country. Genetic variance for SRH increased as financial strain increased, matching the predictions of the diathesis–stress and social comparison models for components of variance. Under these models, environmental improvements would be expected to reduce genetically based health disparities.

Genetics of Attention-Deficit Hyperactivity Disorder.

Attention-Deficit Hyperactivity Disorder (ADHD) has long been recognized as being a highly heritable condition and our understanding of the genetic contributions to ADHD has grown over the past few decades. This chapter will discuss the studies that have examined its heritability and the efforts to identify specific genetic risk-variants at the molecular genetic level. We outline the various techniques that have been used to characterize genetic contributions to ADHD, describing what we have learnt so far, what there is still to learn and the methodologies that can be used to further our knowledge. In doing so we will discuss research into rare and common genetic variants, polygenic risk scores, and gene-environment interplay, while also describing what genetic studies have revealed about the biological processes involved in ADHD and what they have taught us about the overlap between ADHD and other psychiatric and somatic disorders. Finally, we will discuss the strengths and limitations of the current methodologies and clinical implications of genetic research to date.

The Economics and Econometrics of Gene-Environment Interplay

Economists and social scientists have debated the relative importance of nature (one's genes) and nurture (one's environment) for decades, if not centuries. This debate can now be informed by the ready availability of genetic data in a growing number of social science datasets. This paper explores the potential uses of genetic data in economics, with a focus on estimating the interplay between nature (genes) and nurture (environment). We discuss how economists can benefit from incorporating genetic data into their analyses even when they do not have a direct interest in estimating genetic effects. We argue that gene--environment (GxE) studies can be instrumental for (i) testing economic theory, (ii) uncovering economic or behavioral mechanisms, and (iii) analyzing treatment effect heterogeneity, thereby improving the understanding of how (policy) interventions affect population subgroups. We introduce the reader to essential genetic terminology, develop a conceptual economic model to interpret gene-environment interplay, and provide practical guidance to empirical researchers.

The Economics and Econometrics of Gene–Environment Interplay

The Economics and Econometrics of Gene–Environment Interplay

The influence of harshness and unpredictability on female sexual development: Addressing gene-environment interplay using a polygenic score.

Recent developments in the application life history theory to human development indicate two fundamental dimension of the early environment - harshness and unpredictability - are key regulators life history strategies. Few studies have examined the manner with which these dimensions influence development, though age at menarche (AAM) and age at first sexual intercourse have been proposed as possible mechanisms among women. Data from the Avon Longitudinal Study of Parents and Children (N = 3,645) were used to examine direct and indirect effects of harshness (financial difficulties) and unpredictability (paternal transitions) on lifetime and past year sexual partners during adolescence and young adulthood. Genetic confounding was addressed using an AAM polygenic score (PGS) and potential gene-by-environment interactions were also evaluated using the PGS. Path model results showed only harshness was directly related to AAM. Harshness, unpredictability, and AAM were indirectly related to lifetime and past year sexual partner number via age at first sexual intercourse. The PGS did not account for any of the associations and no significant interactions were detected. Implications of these results for developmental models derived from life history theory are discussed as well as the role of PGSs in gene-environment interplay research.

The Heritability of Cognitive Aging: A Systematic Review of Longitudinal Twin Studies

Heritability of cognitive ability changes across late adulthood, although whether genetic variance increases or decreases in importance is not understood well. We performed a systematic review of the heritability of cognitive ability derived from longitudinal twin studies of middle-aged and older adult twins. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles were identified in APA PsycINFO and Clarivate Web of Science electronic databases. Identified articles were screened by title and abstract; remaining full-text articles were then fully evaluated. Reference sections served as an additional method for identification of relevant articles. In total, 3,106 articles were identified and screened, 28 of which were included and were based on data from 10 longitudinal twin studies published from 1994-2021. There are large genetic influences on an initial level of cognitive performance across domains whereas there are small to moderate genetic influences on change in performance with age. Evidence was less definitive about whether the same or different genetic factors contribute to both level and change. Non-shared environmental influences appeared to drive individual changes in cognitive performance. Heritability tended to either be stable or decline after 65 years, possibly because of the increasing importance of non-shared environmental influences on cognitive ability. Recent studies report increases in heritability across specific subtests and domains. Shared environmental variance accounted for little variance in cognitive ability. Emerging research questions and future directions for understanding genetic and environment influences in the context of gene-environment interplay are highlighted in this review.

Michael Rutter: the UK’s first professor of child psychiatry

Photo credit: Corbin O’Grady Studio/SPL The so called father of child psychiatry, Michael Rutter (“Mike”) led the first research into psychiatric and physical disorders in children where researchers spoke directly...

Gene-environment interplay A revolution for social science research?

Gene-environment interplay A revolution for social science research?

A gene-environment interplay between omega-3 supplementation and APOE ε4 provides insights for Alzheimer's disease precise prevention amongst high-genetic-risk population.

The present study aimed to explore whether and how omega-3 (ω-3) supplementation could interact with genetic factors to modulate cognitive functions, amyloid pathologies, and Alzheimer's disease (AD) risk. A total of 1,670 non-demented participants (mean age 73years, 47% females, 41% APOE ε4 carriers) were followed up for 10years. Hierarchical regressions, linear mixed-effects models, and Cox proportional hazards models were used to examine the interaction effects of ω-3 supplementation with APOE ε4 and polygenic hazard scores, after adjusting for age, gender, education, cognitive diagnosis, insomnia, depression, anxiety, and cardiovascular risk score. Individuals who progress to AD during the follow-up tend to take a shorter duration of ω-3 at baseline than those stable, for whom the difference remained significant only amongst APOE ε4 carriers (p<0.01). The interaction term (APOE ε4×ω-3) accounted for a significant amount of variance in cognition and cerebral amyloid burden. Long-term ω-3 use protected cognition (especially memory function) and lowered amyloid burden and AD risk only amongst APOE ε4 carriers. Mediation analysis suggested that amyloid pathologies, brain reserve capacities, and brain metabolism mediated the relationships of ω-3 use with memory and global cognition for APOE ε4 (+) carriers. Similar interaction and mediation effects were also indicated amongst high-risk subjects defined by polygenic hazard scores. Long-term ω-3 intake may have a role in AD prevention in genetically at-risk populations.

Genetic dissection of seasonal vegetation index dynamics in maize through aerial based high-throughput phenotyping.

Plant phenotyping under field conditions plays an important role in agricultural research. Efficient and accurate high-throughput phenotyping strategies enable a better connection between genotype and phenotype. Unmanned aerial vehicle-based high-throughput phenotyping platforms (UAV-HTPPs) provide novel opportunities for large-scale proximal measurement of plant traits with high efficiency, high resolution, and low cost. The objective of this study was to use time series normalized difference vegetation index (NDVI) extracted from UAV-based multispectral imagery to characterize its pattern across development and conduct genetic dissection of NDVI in a large maize population. The time series NDVI data from the multispectral sensor were obtained at five time points across the growing season for 1,752 diverse maize accessions with a UAV-HTPP. Cluster analysis of the acquired measurements classified 1,752 maize accessions into two groups with distinct NDVI developmental trends. To capture the dynamics underlying these static observations, penalized-splines (P-splines) model was used to obtain genotype-specific curve parameters. Genome-wide association study (GWAS) using static NDVI values and curve parameters as phenotypic traits detected signals significantly associated with the traits. Additionally, GWAS using the projected NDVI values from the P-splines models revealed the dynamic change of genetic effects, indicating the role of gene-environment interplay in controlling NDVI across the growing season. Our results demonstrated the utility of ultra-high spatial resolution multispectral imagery, as that acquired using a UAV-based remote sensing, for genetic dissection of NDVI.

Socioeconomic Background and Gene–Environment Interplay in Social Stratification across the Early Life Course

AbstractTo what extent are differences in education, occupational standing, and income attributable to genes, and do genetic influences differ by parents’ socioeconomic standing? When in a children’s life course does parents’ socioeconomic standing matter for genetic influences, and for which of the outcomes, fixed at the different stages of the attainment process, do they matter most? We studied these research questions using Finnish register-based data on 6,529 pairs of twins born between 1975 and 1986. We applied genetically sensitive variance decompositions and took gene–environment interactions into account. Since zygosity was unknown, we compared same-sex and opposite-sex twins to estimate the proportion of genetic variation. Genetic influences were strongest in education and weakest in income, and always strongest among those with the most advantaged socioeconomic background, independent of the socioeconomic indicator used. We found that the shared environment influences were negligible for all outcomes. Parental social background measured early during childhood was associated with weaker interactions with genetic influences. Genetic influences on children’s occupation were largely mediated through their education, whereas for genetic influences on income, mediation through education and occupational standing made little difference. Interestingly, we found that non-shared environment influences were greater among the advantaged families and that this pattern was consistent across outcomes. Stratification scholars should therefore emphasize the importance of the non-shared environment as one of the drivers of the intergenerational transmission of social inequalities.