Associations Between Alcohol Use Disorder Polygenic Score And remission In Participants From High-risk Families And The Indiana Biobank

A prior study indicated a positive correlation between a polygenic score for AUD (PGSAUD) and the severity of AUD symptoms, as measured by the DSM-5 lifetime criterion count. Moreover, the severity of AUD symptoms was inversely related to the likelihood of achieving remission. Building on these findings, the researchers hypothesized that the PGSAUD might also be associated with a reduced likelihood of remission. The study involved individuals of European (EA) and African ancestry (AA) from the Collaborative Study on the Genetics of Alcoholism (COGA) who met the lifetime criteria for AUD. Additionally, two cohorts of individuals of European ancestry were included: one ascertained for studies of liver diseases and the other for substance use disorders from the Indiana Biobank.  

In the COGA group, the definition of 12-month remission was any period of at least 12 consecutive months without meeting AUD criteria except for craving, further categorized as abstinent and non-abstinent remission. Covariates included sex and age, with additional adjustments in COGA analyses for AUD severity, family history of remission, and AUD treatment history. The results in COGA individuals of European ancestry revealed a negative association between PGSAUD and both 12-month and non-abstinent remission, even after adjusting for covariates. However, results in the Indiana Biobank cohorts were inconsistent. In the liver diseases cohort, PGSAUD was positively associated with remission, while in the substance use disorder cohort, no significant association was found.  

PGSAUD was found to be negatively linked to remission in COGA individuals of European ancestry, independent of behavioral measures of AUD severity and family history of remission. The conflicting results between COGA and the Indiana Biobank cohorts may stem from different participant selection criteria, as individuals in the Indiana Biobank cohorts were older and had higher rates of liver disease, suggesting that their remission might be attributed to alcohol-related health conditions emerging later in life. 

 

Lai D, Kuo SI, Wetherill L, Aliev F, Zhang M, Marco A, Schwantes-An TH, Dick D, Francis MW, Johnson EC, Kamarajan C, Kinreich S, Kuperman S, Meyers J, Nurnberger JI, Liu Y, Edenberg HJ, Porjesz B, Agrawal A, Foroud T, Schuckit M, Plawecki MH, Bucholz KK, McCutcheon VV (2024) Associations between alcohol use disorder polygenic score and remission in participants from high-risk families and the Indiana Biobank. Alcohol: Clinical and Experimental Research, 48(2), 283-294. PMID: 38054532DOI: 10.1111/acer.15239.