Characterization of a missense variant in the fatty acid amide hydrolase gene (FAAH) in subjective response to alcohol and related traits in a sample of nondependent social drinkers and individuals seeking treatment for alcohol dependence

Authors

• J Yan
• BL Stangl
• ML Schwandt
• J Westman
• P Spagnolo
• C Hodgkinson
• D Goldman
• DT George
• R Momenan
• VA Ramchandani

Abstract

A functional missense variant, rs324420, in the FAAH gene has been associated with amygdala habituation to threat, anxiety, fear extinction, stress reactivity and reward-related activity. The A allele of rs324420 confers decreased FAAH enzyme, which breaks down the endocannabinoid anandamide; thus, it is hypothesized to increase brain anandamide signaling and potentiate reward responses to alcohol. In order to investigate pathways in which this variant plays in alcohol response, we aimed to characterize its effect on alcohol-related phenotypes and its interaction with childhood adversity in a sample of alcohol dependent treatment-seekers and non-treatment-seeking drinkers (n=1170). A subset of non-treatment-seekers participated in an intravenous alcohol self-administration (IV-ASA) study (n=82), wherein participants press a button to self-administer alcohol via IV, providing greater control over brain exposure than oral intake. Association analyses were performed using linear and logistic models with sex, age, and ancestry covariates. Adversity was measured using the Childhood Trauma Questionnaire (CTQ). Outcomes included alcohol consumption and problems, subjective response to alcohol, and breath alcohol concentration reached during the IV-ASA. The A allele was associated with increased average number of drinks consumed and number of heavy drinking days (p

Scientific Focus Area: Genetics and Genomics

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