The aggregate effect of dopamine genes on dependence symptoms among cocaine users: cross-validation of a candidate system scoring approach.

Behavior Genetics
Jaime DerringerLaura J Bierut

Abstract

Genome-wide studies of psychiatric conditions frequently fail to explain a substantial proportion of variance, and replication of individual SNP effects is rare. We demonstrate a selective scoring approach, in which variants from several genes known to directly affect the dopamine system are considered concurrently to explain individual differences in cocaine dependence symptoms. 273 SNPs from eight dopamine-related genes were tested for association with cocaine dependence symptoms in an initial training sample. We identified a four-SNP score that accounted for 0.55% of the variance in a separate testing sample (p = 0.037). These findings suggest that (1) limiting investigated SNPs to those located in genes of theoretical importance improves the chances of identifying replicable effects by reducing statistical penalties for multiple testing, and (2) considering top-associated SNPs in the aggregate can reveal replicable effects that are too small to be identified at the level of individual SNPs.

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Citations

Jan 13, 2016·Development and Psychopathology·Kaitlin BountressKathryn Lemery-Chalfant
Jan 12, 2016·Substance Abuse : Official Publication of the Association for Medical Education and Research in Substance Abuse·Neeru GoyalDanielle M Dick
Jan 28, 2014·Alcoholism, Clinical and Experimental Research·Daniel E IronsMatt McGue
Nov 18, 2014·Current Psychiatry Reports·Priya A Iyer-Eimerbrink, John I Nurnberger
Apr 14, 2021·Brain, Behavior and Evolution·F Scott HallFederico Resendiz-Gutierrez

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