title: PER1 rs3027172 Genotype Interacts with Early Life Stress to Predict Problematic Alcohol Use, but Not Reward-Related Ventral Striatum Activity.
abstract: Increasing evidence suggests that the circadian and stress regulatory systems contribute to alcohol use disorder (AUD) risk, which may partially arise through effects on reward-related neural function. The C allele of the PER1 rs3027172 single nucleotide polymorphism (SNP) reduces PER1 expression in cells incubated with cortisol and has been associated with increased risk for adult AUD and problematic drinking among adolescents exposed to high levels of familial psychosocial adversity. Using data from undergraduate students who completed the ongoing Duke Neurogenetics Study (DNS) (n = 665), we tested whether exposure to early life stress (ELS; Childhood Trauma Questionnaire) moderates the association between rs3027172 genotype and later problematic alcohol use (Alcohol Use Disorders Identification Test) as well as ventral striatum (VS) reactivity to reward (card-guessing task while functional magnetic resonance imaging data were acquired). Initial analyses found that PER1 rs3027172 genotype interacted with ELS to predict both problematic drinking and VS reactivity; minor C allele carriers, who were also exposed to elevated ELS reported greater problematic drinking and exhibited greater ventral striatum reactivity to reward-related stimuli. When gene × covariate and environment × covariate interactions were controlled for, the interaction predicting problematic alcohol use remained significant (p < 0.05, corrected) while the interaction predicting VS reactivity was no longer significant. These results extend our understanding of relationships between PER1 genotype, ELS, and problematic alcohol use, and serve as a cautionary tale on the importance of controlling for potential confounders in studies of moderation including gene × environment interactions.
authors.affiliation: Brain Laboratory, Department of Psychological and Brain Sciences, Washington University in St. LouisSt. Louis, MO, USA; Division of Biology and Biomedical Sciences, Washington University in St. LouisSt. Louis, MO, USA.
authors.forename: David A A
authors.initials: DA
authors.lastname: Baranger
authors.affiliation: Brain Laboratory, Department of Psychological and Brain Sciences, Washington University in St. Louis St. Louis, MO, USA.
authors.forename: Chloé
authors.initials: C
authors.lastname: Ifrah
authors.affiliation: Department of Psychiatry, University of California, San Francisco San Francisco, CA, USA.
authors.forename: Aric A
authors.initials: AA
authors.lastname: Prather
authors.affiliation: Brain Laboratory, Department of Psychological and Brain Sciences, Washington University in St. Louis St. Louis, MO, USA.
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Carey
authors.affiliation: Department of Psychiatry, Washington University in St. Louis St. Louis, MO, USA.
authors.forename: Nadia S
authors.initials: NS
authors.lastname: Corral-Frías
authors.affiliation: 23andMe Mountain View, CA, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Drabant Conley
authors.affiliation: Laboratory of NeuroGenetics, Department of Psychology and Neuroscience, Duke University Durham, NC, USA.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Hariri
authors.affiliation: Brain Laboratory, Department of Psychological and Brain Sciences, Washington University in St. LouisSt. Louis, MO, USA; Division of Biology and Biomedical Sciences, Washington University in St. LouisSt. Louis, MO, USA; Department of Psychiatry, Washington University in St. LouisSt. Louis, MO, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Bogdan
keywords: GxE; PER1; alcohol; circadian; early life stress; stress; ventral striatum