Addiction. 2021 Apr 16. doi: 10.1111/add.15511. Online ahead of print.
ABSTRACT
BACKGROUND AND AIMS: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire screens for harmful drinking using a 12-month timeframe. A score of 0 is assigned to individuals who report abstaining from alcohol in the past year. However, many middle-aged individuals reporting current abstinence are former drinkers (FDs). Because FDs may be more genetically prone to harmful alcohol use than life-long abstainers (LAs) and are often combined with LAs, we evaluated the impact of differentiating them on the identification of genetic association.
DESIGN AND SETTING: The UK Biobank (UKBB) includes AUDIT-C and alcohol drinker status.
PARTICIPANTS: 131,510 Europeans, including 5,135 FDs.
MEASUREMENTS: We compared three genome-wide association (GWAS) analyses to explore the effects of removing FDs: the full AUDIT-C data, AUDIT-C data without FDs, and data from a random sample numerically matched to the data without FDs. Because prior studies show a consistent association of the ADH1B polymorphism rs1229984 with both alcohol consumption and alcohol use disorder, we compared allele frequencies for rs1229984 stratified by AUDIT-C value and FD versus LA status. Additionally, we calculated polygenic risk scores (PRS) of related diseases.
FINDINGS: The rs1229984 allele frequencies among FDs were numerically comparable to those with high AUDIT-C scores and very different from those of LAs. Removing FDs from GWAS yielded a stronger association with rs1229984 (p-value after removal: 1.9 x10-70 versus 1.7×10-65 and 2.5 x10-62 ), more statistically significant single nucleotide polymorphisms (SNPs) (after removal: 11 versus 9 and 8), and genomic loci (after removal: 11 versus 9 and 7). Additional independent SNPs were identified after removal of FDs: rs2817866 (PTGER3), rs7105867 (ANO3), and rs17601612 (DRD2). For PRS of alcohol use disorder and major depressive disorder, there are statistically significant differences between FDs and LAs.
CONCLUSIONS: Differentiating between former drinkers and life-long abstainers can improve Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) genome-wide association results.
PMID:33861876 | DOI:10.1111/add.15511
