scholarly journals Affiliation with substance-using peers: Examining gene-environment correlations among parent monitoring, polygenic risk, and children's impulsivity

2017 ◽  
Vol 59 (5) ◽  
pp. 561-573 ◽  
Author(s):  
Kit K. Elam ◽  
Laurie Chassin ◽  
Kathryn Lemery-Chalfant ◽  
Danielle Pandika ◽  
Frances L. Wang ◽  
...  
Keyword(s):  
Polygenic Risk ◽  
Gene Environment ◽  
Parent Monitoring

scholarly journals Polygenic interactions with environmental adversity in the aetiology of major depressive disorder

2015 ◽  
Vol 46 (4) ◽  
pp. 759-770 ◽  
Author(s):  
N. Mullins ◽  
R. A. Power ◽  
H. L. Fisher ◽  
K. B. Hanscombe ◽  
J. Euesden ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Environmental Risk ◽  
Complex Traits ◽  
Risk Scores ◽  
Environment Interaction ◽  
Inverse Association ◽  
Major Depressive ◽  
Polygenic Risk ◽  
Gene Environment

BackgroundMajor depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.MethodThe RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.ResultsPRS significantly predicted depression, explaining 1.1% of variance in phenotype (p= 1.9 × 10−6). SLEs and CT were also associated with MDD status (p= 2.19 × 10−4andp= 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p= 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.ConclusionsCT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.

scholarly journals Effect of polygenic risk scores on depression in childhood trauma

2014 ◽  
Vol 205 (2) ◽  
pp. 113-119 ◽  
Author(s):  
Wouter J. Peyrot ◽  
Yuri Milaneschi ◽  
Abdel Abdellaoui ◽  
Patrick F. Sullivan ◽  
Jouke J. Hottenga ◽  
...  
Keyword(s):  
Childhood Trauma ◽  
Meta Analysis ◽  
Genetic Effect ◽  
Risk Scores ◽  
Environment Interaction ◽  
Polygenic Risk ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Genome Wide ◽  
Direct Genetic Effect

BackgroundResearch on gene×environment interaction in major depressive disorder (MDD) has thus far primarily focused on candidate genes, although genetic effects are known to be polygenic.AimsTo test whether the effect of polygenic risk scores on MDD is moderated by childhood trauma.MethodThe study sample consisted of 1645 participants with a DSM-IV diagnosis of MDD and 340 screened controls from The Netherlands. Chronic or remitted episodes (severe MDD) were present in 956 participants. The occurrence of childhood trauma was assessed with the Childhood Trauma Interview and the polygenic risk scores were based on genome-wide meta-analysis results from the Psychiatric Genomics Consortium.ResultsThe polygenic risk scores and childhood trauma independently affected MDD risk, and evidence was found for interaction as departure from both multiplicativity and additivity, indicating that the effect of polygenic risk scores on depression is increased in the presence of childhood trauma. The interaction effects were similar in predicting all MDD risk and severe MDD risk, and explained a proportion of variation in MDD risk comparable to the polygenic risk scores themselves.ConclusionsThe interaction effect found between polygenic risk scores and childhood trauma implies that (1) studies on direct genetic effect on MDD gain power by focusing on individuals exposed to childhood trauma, and that (2) individuals with both high polygenic risk scores and exposure to childhood trauma are particularly at risk for developing MDD.

scholarly journals Genetics of addictive behavior: the example of nicotine dependence

2017 ◽  
Vol 19 (3) ◽  
pp. 237-245 ◽  
Keyword(s):  
Lung Cancer ◽  
Nicotine Dependence ◽  
Genome Wide Association Study ◽  
Environment Interaction ◽  
Addictive Disorders ◽  
Gene Environment ◽  
Genome Wide ◽  
A Genome ◽  
Significant Heritability ◽  
Parent Monitoring

The majority of addictive disorders have a significant heritability—roughly around 50%. Surprisingly, the most convincing association (a nicotinic acetylcholine receptor CHRNA5-A3-B4 gene cluster in nicotine dependence), with a unique attributable risk of 14%, was detected through a genome-wide association study (GWAS) on lung cancer, although lung cancer has a low heritability. We propose some explanations of this finding, potentially helping to understand how a GWAS strategy can be successful. Many endophenotypes were also assessed as potentially modulating the effect of nicotine, indirectly facilitating the development of nicotine dependence. Challenging the involved phenotype led to the demonstration that other potentially overlapping disorders, such as schizophrenia and Parkinson disease, could also be involved, and further modulated by parent monitoring or the existence of a smoking partner. Such a complex mechanism of action is compatible with a gene-environment interaction, most clearly explained by epigenetic factors, especially as such factors were shown to be, at least partly, genetically driven.

scholarly journals Encode and a new landscape for psychiatric genetics

2013 ◽  
Vol 203 (2) ◽  
pp. 84-85 ◽  
Author(s):  
Akshay Nair ◽  
Robert Howard
Keyword(s):  
Gene Regulation ◽  
Environment Interaction ◽  
Psychiatric Genetics ◽  
Encode Project ◽  
Polygenic Risk ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Rigorous Research ◽  
Dna Elements ◽  
Insight Into

SummaryDespite rigorous research into the genetics of neuropsychiatric disorders, the mechanism by which polygenic risk leads to complex clinical phenotypes remains unclear. The Encyclopedia of DNA Elements (ENCODE) project gives us new insight into gene regulation, and gene–gene and gene–environment interaction.Better understanding of these key genomic mechanisms may provide the answers we have been searching for.

scholarly journals Child maltreatment, adaptive functioning, and polygenic risk: A structural equation mixture model

2019 ◽  
Vol 31 (02) ◽  
pp. 443-456 ◽  
Author(s):  
Eric L. Thibodeau ◽  
Katherine E. Masyn ◽  
Fred A. Rogosch ◽  
Dante Cicchetti
Keyword(s):  
Child Maltreatment ◽  
Mixture Model ◽  
Structural Equation ◽  
Latent Class ◽  
Adaptive Functioning ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Gene Environment ◽  
Withdrawn Behavior ◽  
Main Effects

AbstractThis study used a structural equation mixture model to examine associations between child maltreatment, polygenic risk, and indices of adaptive functioning. Children aged 6 to 13 years (N = 1,004), half maltreated, half nonmaltreated, were recruited to attend a research day camp. Multi-informant indicators of prosocial behavior, antisocial behavior, withdrawn behavior, and depression were collected and used in a latent class analysis. Four classes emerged, characterizing “well-adjusted,” “externalizing,” “internalizing,” and “socially dominant” groups. Twelve genetic variants, previously reported in the Gene × Environment literature, were modeled as one weighted polygenic risk score. Large main effects between maltreatment and adaptive functioning were observed (Wald = 35.3, df = 3, p < .0001), along with evidence of a small Gene × Environment effect (Wald = 13.5, df = 3, p = .004), adjusting for sex, age, and covariate interaction effects.

scholarly journals Polygenic risk, family cohesion, and adolescent aggression in Mexican American and European American families: Developmental pathways to alcohol use

2018 ◽  
Vol 30 (5) ◽  
pp. 1715-1728 ◽  
Author(s):  
Kit K. Elam ◽  
Laurie Chassin ◽  
Danielle Pandika
Keyword(s):  
Alcohol Use ◽  
Mexican American ◽  
Family Cohesion ◽  
Early Adulthood ◽  
Risk Scores ◽  
European American ◽  
Polygenic Risk ◽  
Adolescent Aggression ◽  
Gene Environment ◽  
Racial Ethnic

AbstractPoor family cohesion and elevated adolescent aggression are associated with greater alcohol use in adolescence and early adulthood. In addition, evocative gene–environment correlations (rGEs) can underlie the interplay between offspring characteristics and negative family functioning, contributing to substance use. Gene–environment interplay has rarely been examined in racial/ethnic minority populations. The current study examined adolescents’ polygenic risk scores for aggression in evocative rGEs underlying aggression and family cohesion during adolescence, their contributions to alcohol use in early adulthood (n = 479), and differences between Mexican American and European American subsamples. Results suggest an evocative rGE between polygenic risk scores, aggression, and low family cohesion, with aggression contributing to low family cohesion over time. Greater family cohesion was associated with lower levels of alcohol use in early adulthood and this association was stronger for Mexican American adolescents compared to European American adolescents. Results are discussed with respect to integration of culture and racial/ethnic minority samples into genetic research and implications for alcohol use.

scholarly journals Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood: testing gene × environment moderation and mediation

2021 ◽  
pp. 1-11
Author(s):  
Laurent Elkrief ◽  
Bochao Lin ◽  
Mattia Marchi ◽  
Mohammad H Afzali ◽  
Tobias Banaschewski ◽  
...  
Keyword(s):  
Psychotic Disorders ◽  
Secondary Analysis ◽  
Cannabis Use ◽  
Sensitivity Analyses ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genetic Vulnerability ◽  
Gene Environment ◽  
Using Data ◽  
The Relationship

Abstract Background It has not yet been determined if the commonly reported cannabis–psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders. Methods We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort. Results PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects. Conclusions These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis–psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.

scholarly journals Parent and peer influences on emerging adult substance use disorder: A genetically informed study

2016 ◽  
Vol 29 (1) ◽  
pp. 121-142 ◽  
Author(s):  
Kaitlin Bountress ◽  
Laurie Chassin ◽  
Kathryn Lemery-Chalfant
Keyword(s):  
Substance Use ◽  
Risk Score ◽  
Genetic Risk ◽  
Community Sample ◽  
Parental Knowledge ◽  
Emerging Adult ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Gene Environment ◽  
Peer Substance Use

AbstractThe present study utilizes longitudinal data from a high-risk community sample to examine the unique effects of genetic risk, parental knowledge about the daily activities of adolescents, and peer substance use on emerging adult substance use disorders (SUDs). These effects are examined over and above a polygenic risk score. In addition, this polygenic risk score is used to examine gene–environment correlation and interaction. The results show that during older adolescence, higher adolescent genetic risk for SUDs predicts less parental knowledge, but this relation is nonsignificant in younger adolescence. Parental knowledge (using mother report) mediates the effects of parental alcohol use disorder (AUD) and adolescent genetic risk on risk for SUD, and peer substance use mediates the effect of parent AUD on offspring SUD. Finally, there are significant gene–environment interactions such that, for those at the highest levels of genetic risk, less parental knowledge and more peer substance use confers greater risk for SUDs. However, for those at medium and low genetic risk, these effects are attenuated. These findings suggest that the evocative effects of adolescent genetic risk on parenting increase with age across adolescence. They also suggest that some of the most important environmental risk factors for SUDs exert effects that vary across level of genetic propensity.

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