Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,958)

Sanchez-Roige, S.; Palmer, A. A.; Fontanillas, P.; Elson, S.; 23andMe Research Team,; Substance Use Disorder Working Group of the Psychiatric Genomics Consortium,; Adams, M. J.; Howard, D. M.; Edenberg, H. J.; Davies, G.; Crist, R. C.; Deary, I.; McIntosh, A. M.; Clarke, T. K.

doi:10.1101/275917

bioRxiv · 10.1101/275917

Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,958)

Sanchez-Roige, S.·Palmer, A. A.·Fontanillas, P.·Elson, S.·23andMe Research Team,·Substance Use Disorder Working Group of the Psychiatric Genomics Consortium,·Adams, M. J.·Howard, D. M.·Edenberg, H. J.·Davies, G.·Crist, R. C.·Deary, I.·McIntosh, A. M.·Clarke, T. K.

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Abstract

Alcohol use disorders (AUD) are common conditions that have enormous social and economic consequences. We obtained quantitative measures using the Alcohol Use Disorder Identification Test (AUDIT) from two population-based cohorts of European ancestry: UK Biobank (UKB; N=121,604) and 23andMe (N=20,328) and performed a genome-wide association study (GWAS) meta-analysis. We also performed GWAS for AUDIT items 1-3, which focus on consumption (AUDIT-C), and for items 4-10, which focus on the problematic consequences of drinking (AUDIT-P). The GWAS meta-analysis of AUDIT total score identified 10 associated risk loci. Novel associations localized to genes including JCAD and SLC39A13; we also replicated previously identified signals in the genes ADH1B, ADH1C, KLB, and GCKR. The dimensions of AUDIT showed positive genetic correlations with alcohol consumption (rg=0.76-0.92) and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) alcohol dependence (rg=0.33-0.63). AUDIT-P and AUDIT-C showed significantly different patterns of association across a number of traits, including psychiatric disorders. AUDIT-P was positively genetically correlated with schizophrenia (rg=0.22, p=3.0x10-10), major depressive disorder (rg=0.26, p=5.6x10-3), and attention-deficit/hyperactivity disorder (ADHD; rg=0.23, p=1.1x10-5), whereas AUDIT-C was negatively genetically correlated with major depressive disorder (rg=-0.24, p=3.7x10-3) and ADHD (rg=-0.10, p=1.8x10-2). We also used the AUDIT data in the UKB to identify thresholds for dichotomizing AUDIT total score that optimize genetic correlations with DSM-IV alcohol dependence. Coding individuals with AUDIT total score of [≤]4 as controls and [≥]12 as cases produced a high genetic correlation with DSM-IV alcohol dependence (rg=0.82, p=3.2x10-6) while retaining most subjects. We conclude that AUDIT scores ascertained in population-based cohorts can be used to explore the genetic basis of both alcohol consumption and AUD.

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Sanchez-Roige, S., Palmer, A. A., Fontanillas, P., Elson, S., 23andMe Research Team,, Substance Use Disorder Working Group of the Psychiatric Genomics Consortium,, Adams, M. J., Howard, D. M., Edenberg, H. J., Davies, G., Crist, R. C., Deary, I., McIntosh, A. M., Clarke, T. K.. 2018-03-06. Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,958). https://doi.org/10.1101/275917

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