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Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,932)

Sandra Sanchez-Roige, Abraham A. Palmer, Pierre Fontanillas, Sarah L. Elson, The 23andMe Research Team, Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, Mark J. Adams, David M. Howard, Howard J. Edenberg, Gail Davies, Richard C. Crist, Ian J. Deary, Andrew M. McIntosh, Toni-Kim Clarke
doi: https://doi.org/10.1101/275917
Sandra Sanchez-Roige
Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA
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Abraham A. Palmer
Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USAInstitute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA
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Pierre Fontanillas
Collaborator List for the 23andMe Research Team: Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, Nicholas A. Furlotte, David A. Hinds, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, Jennifer C. McCreight, Matthew H. McIntyre, Joanna L. Mountain, Elizabeth S. Noblin, Carrie A.M. Northover, Steven J. Pitts, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Joyce Y. Tung, Vladimir Vacic, and Catherine H. Wilson
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Sarah L. Elson
Collaborator List for the 23andMe Research Team: Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, Nicholas A. Furlotte, David A. Hinds, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, Jennifer C. McCreight, Matthew H. McIntyre, Joanna L. Mountain, Elizabeth S. Noblin, Carrie A.M. Northover, Steven J. Pitts, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Joyce Y. Tung, Vladimir Vacic, and Catherine H. Wilson
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Collaborator List for the 23andMe Research Team: Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, Nicholas A. Furlotte, David A. Hinds, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, Jennifer C. McCreight, Matthew H. McIntyre, Joanna L. Mountain, Elizabeth S. Noblin, Carrie A.M. Northover, Steven J. Pitts, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Joyce Y. Tung, Vladimir Vacic, and Catherine H. Wilson
Mark J. Adams
Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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David M. Howard
Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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Howard J. Edenberg
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
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Gail Davies
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UKDepartment of Psychology, University of Edinburgh, Edinburgh, UK
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Richard C. Crist
Translational Research Laboratories, Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
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Ian J. Deary
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UKDepartment of Psychology, University of Edinburgh, Edinburgh, UK
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Andrew M. McIntosh
Division of Psychiatry, University of Edinburgh, Edinburgh, UKCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
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Toni-Kim Clarke
Division of Psychiatry, University of Edinburgh, Edinburgh, UK
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  • For correspondence: toni.clarke@ed.ac.uk
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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=3.0×10−10), major depressive disorder (rg=0.26, p=5.6×10−3), and attention-deficit/hyperactivity disorder (ADHD; rg=0.23, p=1.1×10−5), whereas AUDIT-C was negatively genetically correlated with major depressive disorder (rg=−0.24, p=3.7×10−3) and ADHD (rg=−0.10, p=1.8×10−2). 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=3.2×10−6) 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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Posted August 02, 2018.
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Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,932)
Sandra Sanchez-Roige, Abraham A. Palmer, Pierre Fontanillas, Sarah L. Elson, The 23andMe Research Team, Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, Mark J. Adams, David M. Howard, Howard J. Edenberg, Gail Davies, Richard C. Crist, Ian J. Deary, Andrew M. McIntosh, Toni-Kim Clarke
bioRxiv 275917; doi: https://doi.org/10.1101/275917
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Genome-wide association study meta-analysis of the Alcohol Use Disorder Identification Test (AUDIT) in two population-based cohorts (N=141,932)
Sandra Sanchez-Roige, Abraham A. Palmer, Pierre Fontanillas, Sarah L. Elson, The 23andMe Research Team, Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, Mark J. Adams, David M. Howard, Howard J. Edenberg, Gail Davies, Richard C. Crist, Ian J. Deary, Andrew M. McIntosh, Toni-Kim Clarke
bioRxiv 275917; doi: https://doi.org/10.1101/275917

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