TY - JOUR
T1 - Drinking motives and alcohol sensitivity mediate multidimensional genetic influences on alcohol use behaviors
AU - Spit for Science Working Group
AU - Savage, Jeanne E.
AU - Chartier, Karen
AU - Amstadter, Ananda
AU - Lilley, Emily
AU - Gelzinis, Renolda
AU - Morris, Anne
AU - Bountress, Katie
AU - Adkins, Amy E.
AU - Thomas, Nathaniel
AU - Neale, Zoe
AU - Pedersen, Kimberly
AU - Bannard, Thomas
AU - Cho, Seung B.
AU - Barr, Peter
AU - Byers, Holly
AU - Berenz, Erin C.
AU - Caraway, Erin
AU - Cho, Seung B.
AU - Clifford, James S.
AU - Cooke, Megan
AU - Do, Elizabeth
AU - Edwards, Alexis C.
AU - Goyal, Neeru
AU - Hack, Laura M.
AU - Halberstadt, Lisa J.
AU - Hawn, Sage
AU - Kuo, Sally
AU - Lasko, Emily
AU - Lend, Jennifer
AU - Lind, Mackenzie
AU - Long, Elizabeth
AU - Martelli, Alexandra
AU - Meyers, Jacquelyn L.
AU - Mitchell, Kerry
AU - Moore, Ashlee
AU - Moscati, Arden
AU - Nasim, Aashir
AU - Opalesky, Jill
AU - Overstreet, Cassie
AU - Pais, A. Christian
AU - Raldiris, Tarah
AU - Salvatore, Jessica
AU - Smith, Rebecca
AU - Sosnowski, David
AU - Su, Jinni
AU - Walker, Chloe
AU - Walsh, Marcie
AU - Willoughby, Teresa
AU - Woodroof, Madison
AU - Yan, Jia
N1 - Publisher Copyright:
© 2025 The Author(s). Alcohol, Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.
PY - 2025/5
Y1 - 2025/5
N2 - Background: Genetic influences account for a substantial proportion of individual differences in alcohol use behaviors (AUBs). However, multiple distinct sets of genes are linked to different AUBs via uncertain causal links. Here, we explore whether intermediate neurobiological traits mediate the relationship between polygenic scores (PGSs) and multiple AUBs, with the aim to better understand processes captured by different genetic profiles. Methods: We derived four alcohol-related PGSs in participants from Spit for Science, a longitudinal study of college students in the United States (n = 4549). Using linear regression, we tested the relationship between PGSs and 22 potential mediators, including personality, alcohol expectancies, drinking motives, and alcohol sensitivity. Nominally significant effects were carried forward to a multiple mediation model to estimate direct and indirect effects on four measured AUBs (frequency, quantity, alcohol use disorder symptoms [AUDsx], and maximum drinks in 24 h). Results: In univariable regression, PGSs indexing genetic effects on drinks per week (DPW) and problematic alcohol use (PAU) predicted higher levels of impulsivity and drinking motives as well as lower alcohol sensitivity. BeerPref PGSs (indexing a variable pattern of alcohol problems and preference for beer) predicted higher negative urgency and lower alcohol sensitivity. Mediational models indicated direct and indirect effects of DPW PGSs on multiple AUBs via social/enhancement drinking motives and alcohol sensitivity, indirect effects of PAU PGSs on AUDsx, and indirect effects of BeerPref PGS on drinking frequency and AUDsx via the joint effect of mediators including alcohol sensitivity. Conclusions: These findings provide evidence that the genetic influences on AUBs are associated with and partially mediated by intermediate neurobiological and cognitive factors, which may be more amenable to intervention. Greater focus on drinking motives and alcohol sensitivity is warranted in genetic research, as well as attention to the heterogeneous pathways linking genes to alcohol use outcomes.
AB - Background: Genetic influences account for a substantial proportion of individual differences in alcohol use behaviors (AUBs). However, multiple distinct sets of genes are linked to different AUBs via uncertain causal links. Here, we explore whether intermediate neurobiological traits mediate the relationship between polygenic scores (PGSs) and multiple AUBs, with the aim to better understand processes captured by different genetic profiles. Methods: We derived four alcohol-related PGSs in participants from Spit for Science, a longitudinal study of college students in the United States (n = 4549). Using linear regression, we tested the relationship between PGSs and 22 potential mediators, including personality, alcohol expectancies, drinking motives, and alcohol sensitivity. Nominally significant effects were carried forward to a multiple mediation model to estimate direct and indirect effects on four measured AUBs (frequency, quantity, alcohol use disorder symptoms [AUDsx], and maximum drinks in 24 h). Results: In univariable regression, PGSs indexing genetic effects on drinks per week (DPW) and problematic alcohol use (PAU) predicted higher levels of impulsivity and drinking motives as well as lower alcohol sensitivity. BeerPref PGSs (indexing a variable pattern of alcohol problems and preference for beer) predicted higher negative urgency and lower alcohol sensitivity. Mediational models indicated direct and indirect effects of DPW PGSs on multiple AUBs via social/enhancement drinking motives and alcohol sensitivity, indirect effects of PAU PGSs on AUDsx, and indirect effects of BeerPref PGS on drinking frequency and AUDsx via the joint effect of mediators including alcohol sensitivity. Conclusions: These findings provide evidence that the genetic influences on AUBs are associated with and partially mediated by intermediate neurobiological and cognitive factors, which may be more amenable to intervention. Greater focus on drinking motives and alcohol sensitivity is warranted in genetic research, as well as attention to the heterogeneous pathways linking genes to alcohol use outcomes.
KW - drinking motives
KW - genetic heterogeneity
KW - level of response to alcohol
KW - mediation
KW - polygenic scores
UR - https://www.scopus.com/pages/publications/105002437173
UR - https://www.scopus.com/pages/publications/105002437173#tab=citedBy
U2 - 10.1111/acer.70045
DO - 10.1111/acer.70045
M3 - Article
AN - SCOPUS:105002437173
SN - 0145-6008
VL - 49
SP - 1001
EP - 1012
JO - Alcohol, Clinical and Experimental Research
JF - Alcohol, Clinical and Experimental Research
IS - 5
ER -