Mechanisms of parent–child transmission of tobacco and alcohol use with polygenic risk scores: Evidence for a genetic nurture effect.

2021 ◽  
Vol 57 (5) ◽  
pp. 796-804
Author(s):  
Gretchen R. B. Saunders ◽  
◽  
Mengzhen Liu ◽  
Scott Vrieze ◽  
Matt McGue ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Risk Scores ◽  
Child Transmission ◽  
Polygenic Risk ◽  
Parent Child

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 Genome-wide Association Study of Alcohol Consumption and Use Disorder in Multiple Populations (N = 274,424)

2019 ◽  
Author(s):  
Henry R. Kranzler ◽  
Hang Zhou ◽  
Rachel L. Kember ◽  
Rachel Vickers Smith ◽  
Amy C. Justice ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Genome Wide Association ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Cell Type ◽  
Polygenic Risk ◽  
Consumption Level ◽  
Genome Wide

SummaryAlthough alcohol consumption level and alcohol use disorder (AUD) diagnosis are both moderately heritable, their genetic risks and overlap are not well understood. We conducted genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores (reflecting alcohol consumption) and AUD diagnoses from electronic health records (EHRs) in a single, large multi-ancestry Million Veteran Program sample. Meta-analysis across population groups (N = 274,424) identified 18 genome-wide significant loci, 5 of which were associated with both traits and 13 with either AUDIT-C (N = 8) or AUD (N = 5). A significant genetic correlation between the traits reflects this overlap. However, downstream analyses revealed biologically meaningful points of divergence. Cell-type group partitioning heritability enrichment analyses indicated that central nervous system was the most significant cell type for AUDIT-C and the only significant cell type for AUD. Polygenic risk scores (PRS) for both traits were associated with alcohol-related disorders in two independent samples. Genetic correlations for 188 non-alcohol-related traits were significantly different for the two traits, as were the phenotypes associated with the traits’ polygenic risk scores. We conclude that EHR-derived, longitudinal, repeated measures of alcohol consumption level and AUD diagnosis can facilitate genetic discovery and help to elucidate the relationship between drinking level and AUD risk. Finally, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder.

scholarly journals Genetic and shared couple environmental contributions to smoking and alcohol use in the UK population

2019 ◽  
Author(s):  
Toni-Kim Clarke ◽  
Mark J. Adams ◽  
David M. Howard ◽  
Charley Xia ◽  
Gail Davies ◽  
...  
Keyword(s):  
Substance Use ◽  
Alcohol Use ◽  
Environmental Factors ◽  
Assortative Mating ◽  
Family Environment ◽  
Alcohol Intake ◽  
Risk Scores ◽  
Phenotypic Variance ◽  
Polygenic Risk ◽  
The Uk

AbstractAlcohol use and smoking are leading causes of death and disability worldwide. Both genetic and environmental factors have been shown to influence individual differences in the use of these substances. In the present study we tested whether genetic factors, modelled alongside common family environment, explained phenotypic variance in alcohol use and smoking behaviour in the Generation Scotland (GS) family sample of up to 19,377 individuals. SNP and pedigree-associated effects combined explained between 18 and 41% of the variance in substance use. Shared couple effects explained a significant amount of variance across all substance use traits, particularly alcohol intake, for which 38% of the phenotypic variance was explained. We tested whether the within-couple substance use associations were due to assortative mating by testing the association between partner polygenic risk scores in 34,987 couple pairs from the UK Biobank (UKB). No significant association between partner polygenic risk scores were observed. Associations between an individual's alcohol PRS (b = 0.05, S.E. = 0.006, p < 2 × 10−16) and smoking status PRS (b = 0.05, S.E. = 0.005, p < 2 × 10−16) were found with their partner’s phenotype. In support of this, G carriers of a functional ADH1B polymorphism (rs1229984), known to be associated with greater alcohol intake, were found to consume less alcohol if they had a partner who carried an A allele at this SNP. Together these results show that the shared couple environment contributes significantly to patterns of substance use. It is unclear whether this is due to shared environmental factors, assortative mating, or indirect genetic effects. Future studies would benefit from longitudinal data and larger sample sizes to assess this further.

scholarly journals Age varying polygenic effects on alcohol use in African Americans and European Americans from adolescence to adulthood

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kit K. Elam ◽  
Thao Ha ◽  
Zoe Neale ◽  
Fazil Aliev ◽  
Danielle Dick ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Association Studies ◽  
Genetic Effects ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Longitudinal Models ◽  
Polygenic Risk ◽  
Genome Wide ◽  
Polygenic Scores ◽  
Distal Outcome

AbstractGenetic effects on alcohol use can vary over time but are often examined using longitudinal models that predict a distal outcome at a single time point. The vast majority of these studies predominately examine effects using White, European American (EA) samples or examine the etiology of genetic variants identified from EA samples in other racial/ethnic populations, leading to inconclusive findings about genetic effects on alcohol use. The current study examined how genetic influences on alcohol use varied by age across a 15 year period within a diverse ethnic/racial sample of adolescents. Using a multi-ethnic approach, polygenic risk scores were created for African American (AA, n = 192) and EA samples (n = 271) based on racially/ethnically aligned genome wide association studies. Age-varying associations between polygenic scores and alcohol use were examined from age 16 to 30 using time-varying effect models separately for AA and EA samples. Polygenic risk for alcohol use was found to be associated with alcohol use from age 22–27 in the AA sample and from age 24.50 to 29 in the EA sample. Results are discussed relative to the intersection of alcohol use and developmental genetic effects in diverse populations.

Genome-wide investigation of alcohol response : a meta-analytic review and polygenic associations with alcohol use disorder

2020 ◽  
Author(s):  
◽  
Joseph D. Deak
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Meta Analysis ◽  
Genotype Imputation ◽  
Genetic Influences ◽  
Risk Scores ◽  
Individual Study ◽  
Polygenic Risk ◽  
Gene Set ◽  
Genome Wide

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI-COLUMBIA AT REQUEST OF AUTHOR.] The current study aimed to extend previous genetic studies of level of response (LR) to alcohol by conducting the largest genome-wide association study (GWAS) of LR to date through the meta-analysis of multiple samples with extant SRE (Self-rating of the Effects of Alcohol) and GWAS data. A second aim was to use summary data from the described GWAS of LR to create polygenic risk scores (PRS) in an independent sample in order to determine whether, and to what extent, the genetic influences underlying LR to alcohol serve as a risk factor for alcohol use disorder (AUD). Towards these aims, datasets were processed according to standard quality control (QC) procedures allowing for genotype imputation and GWA analysis using methods appropriate for the individual study designs. Following individual study-level GWAS analysis, results were meta-analyzed utilizing an inverse-variance weighted fixed-effects model in METAL resulting in a final sample size of N=10,635. GWAS summary statistics from the SRE meta-analysis were then used to conduct gene-based and gene-set analyses, as well as compute polygenic risk scores (PRS) in an independent target sample to examine the predictive ability of the LR to alcohol PRS for DSM-IV AD symptom counts. No individual variants, genes, or gene-sets achieved study-level significance, although multiple genetic loci of interest achieved suggestive significance. The top single variant association was in an intergenic region on chromosome 2 located near the FUNDC2P2 gene (rs12463481; p=6.35x10[superscript -8]), the top gene-based association was with the PRR16 gene on chromosome 5 (p=6.72x10 [superscript -6]), and the top gene-set was with a set of genes associated with NFE2L2 targets (p=1.21 x10 [superscript -5]). No results from the PRS analysis approached significance. These findings suggest that, similar to other alcohol use outcomes, larger sample sizes will be required for the robust detection of genetic influences contributing to level of response to alcohol.

scholarly journals Serotonin functioning and adolescents' alcohol use: A genetically informed study examining mechanisms of risk

2017 ◽  
Vol 30 (1) ◽  
pp. 213-233 ◽  
Author(s):  
Frances L. Wang ◽  
Laurie Chassin ◽  
John E. Bates ◽  
Danielle Dick ◽  
Jennifer E. Lansford ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Alcohol Use ◽  
Parental Education ◽  
Genome Wide Association Study ◽  
Self Regulation ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Genome Wide ◽  
Two Samples ◽  
Hydroxyindoleacetic Acid

AbstractThe current study used data from two longitudinal samples to test whether self-regulation, depressive symptoms, and aggression/antisociality were mediators in the relation between a polygenic score indexing serotonin (5-HT) functioning and alcohol use in adolescence. The results from an independent genome-wide association study of 5-hydroxyindoleacetic acid in the cerebrospinal fluid were used to create 5-HT polygenic risk scores. Adolescents and/or parents reported on adolescents’ self-regulation (Time 1), depressive symptoms (Time 2), aggression/antisociality (Time 2), and alcohol use (Time 3). The results showed that 5-HT polygenic risk did not predict self-regulation. However, adolescents with higher levels of 5-HT polygenic risk showed greater depression and aggression/antisociality. Adolescents’ aggression/antisociality mediated the relation between 5-HT polygenic risk and later alcohol use. Deficits in self-regulation also predicted depression and aggression/antisociality, and indirectly predicted alcohol use through aggression/antisociality. Pathways to alcohol use were especially salient for males from families with low parental education in one of the two samples. The results provide insights into the longitudinal mechanisms underlying the relation between 5-HT functioning and alcohol use (i.e., earlier aggression/antisociality). There was no evidence that genetically based variation in 5-HT functioning predisposed individuals to deficits in self-regulation. Genetically based variation in 5-HT functioning and self-regulation might be separate, transdiagnostic risk factors for several types of psychopathology.

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