Genetic Links to the Reinforcing Effects of Alcohol in a Social Context

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DESCRIPTION (provided by applicant): People respond to alcohol differently, and this response variation has been shown to predict increased risk to develop alcohol use disorders (AUD). For instance, individuals who experience more rewarding effects of alcohol during social interactions may be especially likely to misuse alcohol. Researchers have been interested in identifying links between genetic variation and alcohol response, but this objective has proved challenging. Inconsistent findings likely result from the use of small sample sizes and the tendency of researchers to study individuals' response to alcohol while they are in isolation. Social factors play a major role in AUD, yet researchers rarely study the effects of alcohol in a group setting. The proposed project will systematically measure the effects of alcohol on positive and negative affect (using Ekman et al.'s (2002) Facial Action Coding System) during a group interaction. Self-reported mood, social bonding, speech behavior, and subjective intoxication levels will also be assessed. The study will determine if persons with polymorphic variation in genes associated with increased risk for AUD [i.e., genes encoding the serotonin transporter, dopamine D2 and D4 receptors, and the receptor for gamma-aminobutyric acid (GABA)] are more sensitive to alcohol's rewarding effects in a social setting. Social drinkers (n= 720) will be assembled into 240 3-person groups and will drink over 30-min a moderate dose of alcohol (males: 0.82 g/kg; females: 0.74 g/kg), a placebo, or a nonalcoholic control drink. This group drinking period will be recorded using a digital control system that enables precise analysis of the duration and sequence of facial expressions as they unfold over time. The proposed project will be the first with sufficient power to combine human genetic perspectives, social psychological theory, and recent advances in the systematic measurement of observed behavior to determine the genetic links to alcohol response variation in a social context. Alcohol use disorders are associated with multiple adverse health consequences and claim the lives of over 100,000 people each year. Approximately half of the variability in risk to develop AUD is genetic. It is a research priority to identify individuals with increased susceptibility to develop AUD, as such information would greatly inform prevention and treatment strategies. By combining human genotyping with a comprehensive multi-dimensional assessment of alcohol's reinforcing effects in a social context, the mechanisms through which genetic factors influence drinking outcomes in men and women may be elucidated. This information will greatly inform theories of drinking and alcoholism and will help to predict who may be at risk of developing drinking problems.