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Polygenic Predictors of Alcohol Response in Social Drinking Settings

Award Number: R01AA033096
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/03/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Polygenic Predictors of Alcohol Response in Social Drinking Settings - Project Summary / Abstract Alcohol Use Disorder (AUD) is a leading cause of preventable death and disability in the United States. One well- established yet poorly understood risk mechanism is individual variation in acute responses to alcohol (AR), including the degree to which alcohol produces positively and negatively reinforcing effects. Although AR are heritable and predict future AUD risk, decades of research have largely failed to identify specific genetic variants that influence these responses. This gap has persisted in part due to methodological limitations of prior studies, which relied on either underpowered candidate gene designs or large-scale genome-wide association studies (GWAS) that used retrospective and potentially imprecise self-reports of AR. Moreover, nearly all past alcohol administration research has assessed AR in solitary contexts, which are unrepresentative of how alcohol is typically consumed among young adults. As a result, despite longstanding theoretical support, direct evidence linking genetic risk to real-time AR remains elusive. The proposed project leverages two major methodological advances to address this gap: (1) polygenic scores (PGS), which now allow genetic risk for AUD to be reliably estimated in small samples; and (2) ecologically valid, multi- participant alcohol administration paradigms that assess AR in real-time during unscripted social interactions. Using existing data from two of the largest NIAAA-funded alcohol administration studies (N=899), the project integrates genomic data with >55 million coded behavioral observations collected during group drinking sessions. These sessions were video recorded and coded using validated systems to assess AR across multiple modalities (e.g., facial expressions, speech, self-reports). Participants were randomly assigned to drink alcohol, placebo, or control beverages, and their DNA will be genotyped to construct PGS representing three AUD-related risk pathways: sensitivity to alcohol’s acute effects, externalizing traits, and internalizing traits. We will test whether PGS linked to these three major pathways of AUD risk predict variation in alcohol’s positively and negatively reinforcing effects. Exploratory aims will examine whether group- level genetic risk moderates group-level AR, providing a novel test of gene-by-environment interactions in real time. This integrative, interdisciplinary project offers the most rigorous and ecologically valid test to date of whether genetic liability for AUD influences drinking behavior via intermediate AR mechanisms. Findings will inform biologically grounded, personalized prevention strategies aligned with NIAAA’s precision medicine priorities to reduce the burden of alcohol misuse.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $593,733 )
2026	2026	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Alcohol Research Programs	000	1	8/5/2026	NEW	$593,733
														Subtotal = $593,733

Grand Total All Awards = $593,733

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Polygenic Predictors of Alcohol Response in Social Drinking Settings

Award Number: R01AA033096

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/03/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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