AUTHOR=Sheerin Christina M. , O’Hara-Payne Rowan K. , Lancaster Eva E. , Suarez-Rivas Hailie , Spit for Science Working Group , Chatzinakos Chris , Prom-Wormley Elizabeth C. , Peterson Roseann E. , Aliev Fazil , Adkins Amy E. , Amstadter Ananda , Bannard Thomas , Barr Peter , Berenz Erin C. , Bountress Katie , Byers Holly , Christian Pais A. , Caraway Erin , Clifford James S. , Cooke Megan , Chartier Karen , Cho Seung B. , Do Elizabeth , Dick Danielle M. , Edwards Alexis C. , Gelzinis Renolda , Goyal Neeru , Hawn Sage , Hack Laura M. , Halberstadt Lisa J. , Kuo Sally , Meyers Jacquelyn L. , Lasko Emily , Lend Jennifer , Lilley Emily , Lind Mackenzie , Long Elizabeth , Martelli Alexandra , Moscati Arden , Morris Anne , Moore Ashlee , Mitchell Kerry , Nasim Aashir , Neale Zoe , Opalesky Jill , Overstreet Cassie , Pedersen Kimberly , Peterson Roseann E. , Raldiris Tarah , Riley Brien , Salvatore Jessica , Savage Jeanne , Sosnowski David , Smith Rebecca , Su Jinni , Sun Cuie , Thomas Nathaniel , Walker Chloe , Walsh Marcie , Webb Bradley T. , Willoughby Teresa , Wormley Brandon , Woodroof Madison , Yan Jia
TITLE=Examining interactions between polygenic scores and interpersonal trauma exposure on alcohol consumption and use disorder in an ancestrally diverse college cohort
JOURNAL=Frontiers in Genetics
VOLUME=14
YEAR=2024
URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1274381
DOI=10.3389/fgene.2023.1274381
ISSN=1664-8021
ABSTRACT=Introduction: Genetic factors impact alcohol consumption and use disorder (AUD), with large-scale genome-wide association studies (GWAS) identifying numerous associated variants. Aggregate genetic methods in combination with important environmental factors (e.g., interpersonal trauma [IPT]) can be applied to expand our understanding of the ways by which genetic and environmental variables work together to influence alcohol consumption and disordered use. The present study aimed to detail the relationships between genome-wide polygenic scores (PGS) for alcohol phenotypes (i.e., alcohol consumption and AUD status) and IPT exposure as well as the interaction between them across ancestry.
Methods: Data were drawn from the Spit for Science (S4S) study, a US college student population, where participants reported on IPT exposure prior to college and alcohol consumption and problems during college (N = 9,006; ancestry: 21.3% African [AFR], 12.5% Admixed Americas [AMR], 9.6% East Asian [EAS], 48.1% European [EUR], 8.6% South Asian [SAS]). Two trans-ancestry PGS were constructed, one for alcohol consumption and another for AUD, using large-scale GWAS summary statistics from multiple ancestries weighted using PRS-CSx. Regression models were applied to test for the presence of associations between alcohol-PGS and IPT main and interaction effects.
Results: In the meta-analysis across ancestry groups, IPT exposure and PGS were significantly associated with alcohol consumption (βIPT = 0.31, PIPT = 0.0002; βPGS = 0.09, PPGS = 0.004) and AUD (ORIPT = 1.12, PIPT = 3.5 × 10−8; ORPGS = 1.02, PPGS = 0.002). No statistically significant interactions were detected between IPT and sex nor between IPT and PGS. When inspecting ancestry specific results, the alcohol consumption-PGS and AUD-PGS were only statistically significant in the EUR ancestry group (βPGS = 0.09, PPGS = 0.04; ORPGS = 1.02, PPGS = 0.022, respectively).
Discussion: IPT exposure prior to college was strongly associated with alcohol outcomes in this college-age sample, which could be used as a preventative measure to identify students at high risk for problematic alcohol use. Additionally, results add to developing evidence of polygenic score association in meta-analyzed samples, highlighting the importance of continued efforts to increase ancestral representation in genetic studies and inclusive analytic approaches to increase the generalizability of results from genetic association studies.