Yale University School of Public Health, New Haven, CT, USA.
Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
Addiction. 2021 Nov;116(11):3044-3054. doi: 10.1111/add.15511. Epub 2021 May 6.
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-age individuals reporting current abstinence are former drinkers (FDs). Because FDs may be more genetically prone to harmful alcohol use than lifelong abstainers (LAs) and are often combined with LAs, we evaluated the impact of differentiating them on the identification of genetic association.
The United Kingdom Biobank (UKBB) includes AUDIT-C and alcohol drinker status.
131 510 Europeans, including 5135 FDs.
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.
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 × 10 vs 1.7 × 10 and 2.5 × 10 ), more statistically significant single nucleotide polymorphisms (SNPs) (after removal: 11 vs 9 and 8), and genomic loci (after removal: 11 vs 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.
Differentiating between former drinkers and lifelong abstainers can improve Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) genome-wide association results.
酒精使用障碍识别测试-消费（AUDIT-C）问卷使用 12 个月的时间框架筛查有害饮酒。报告过去一年戒酒的个体得分为 0。然而，许多报告目前戒酒的中年人都是前饮酒者（FDs）。由于 FDs 可能比终身戒酒者（LAs）更易遗传地产生有害的饮酒行为，并且通常与 LAs 混合在一起，因此我们评估了区分它们对鉴定遗传关联的影响。
英国生物库（UKBB）包含 AUDIT-C 和饮酒者状况。
131510 名欧洲人，包括 5135 名 FDs。
我们比较了三种全基因组关联（GWAS）分析，以探索去除 FDs 的影响：完整的 AUDIT-C 数据、不包括 FDs 的 AUDIT-C 数据以及与不包括 FDs 的数据数值匹配的随机样本数据。由于先前的研究表明 ADH1B 多态性 rs1229984 与饮酒量和酒精使用障碍都有一致的关联，我们比较了根据 AUDIT-C 值和 FD 与 LA 状态分层的 rs1229984 的等位基因频率。此外，我们计算了相关疾病的多基因风险评分（PRS）。
FDs 中的 rs1229984 等位基因频率在数值上与高 AUDIT-C 评分相似，与 LA 非常不同。从 GWAS 中去除 FDs 会导致与 rs1229984 更强的关联（去除后 P 值：1.9×10-8 与 1.7×10-8 和 2.5×10-8），更多统计学意义上的单核苷酸多态性（SNP）（去除后：11 与 9 和 8）和基因组位点（去除后：11 与 9 和 7）。去除 FDs 后还鉴定出了其他独立的 SNP：rs2817866（PTGER3）、rs7105867（ANO3）和 rs17601612（DRD2）。对于酒精使用障碍和重度抑郁症的 PRS，FDs 与 LAs 之间存在统计学上的显著差异。
区分前饮酒者和终身戒酒者可以改善酒精使用障碍识别测试-消费（AUDIT-C）的全基因组关联结果。
