Multivariate analyses of polygenic risk for impulsivity and alcohol use: a study of longitudinal trajectories of binge drinking in emerging adulthood
No Thumbnail Available
Authors
Meeting name
Sponsors
Date
Journal Title
Format
Thesis
Subject
Abstract
This dissertation aimed to extend previous genetic and neurobiological studies of the shared etiology of impulsive personality traits (IPTs), alcohol consumption and alcohol use disorder (AUD). The overarching goals were to (1) leverage advanced multivariate genome-wide association study (GWAS) approaches to improve current models of neurogenetic liability for IPTs using a dual-systems framework (e.g., top-down lack of self-control, and bottom-up sensation seeking and urgency), and (2) apply improved genetic liability models and polygenic scoring (PGS) techniques to the prediction of changes in binge drinking in developmentally relevant longitudinal samples. Study 1 included several structural, stratified, and genome-wide association analyses using epigenetic, transcriptomic, and neuroimaging datasets. Analyses and data were used to construct and investigate converging and discriminating evidence of dual-systems IPT genetic factor models and shared neurogenetic architecture with alcohol consumption and AUD. GWAS summary statistics generated in Study 1 were utilized in Study 2 to construct dual-systems IPT, alcohol consumption, and AUD PGS variables, which were then specified as predictors in longitudinal analyses of binge drinking progression in three independent longitudinal samples spanning adolescence to early adulthood. Results from Study 1 suggested distinct genetic architecture across tested dual-systems and alcohol use traits, though also indicated robust evidence of a neurobiologically defined shared genetic basis between sensation seeking and alcohol consumption. Study 2 results highlighted important associations between sensation seeking and alcohol consumption PGSs and trajectories of binge drinking across time and samples. In aggregate, these results represent novel findings regarding the genetic architecture of dual-systems IPT constructs and increase understanding of their relevance to alcohol use phenotypes.
Table of Contents
DOI
PubMed ID
Degree
Ph. D.