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Genome-wide association study of Alcohol Use Disorder Identification Test (AUDIT) scores in 20,328 research participants of European ancestry

View ORCID ProfileSandra Sanchez-Roige, Pierre Fontanillas, Sarah L. Elson, the 23 and Me Research Team, Joshua C. Gray, View ORCID ProfileHarriet de Wit, View ORCID ProfileLea K. Davis, View ORCID ProfileJames MacKillop, View ORCID ProfileAbraham A. Palmer
doi: https://doi.org/10.1101/147397
Sandra Sanchez-Roige
1Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA
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  • ORCID record for Sandra Sanchez-Roige
Pierre Fontanillas
223andMe, Inc., Mountain View, CA, USA
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Sarah L. Elson
223andMe, Inc., Mountain View, CA, USA
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223andMe, Inc., Mountain View, CA, USA
Joshua C. Gray
3Department of Psychology, University of Georgia, USA
4Center for Alcohol and Addiction Studies, Brown University School of Public Health, Providence, RI 02903, USA
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Harriet de Wit
5Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL 60637, USA
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Lea K. Davis
6Vanderbilt Genetics Institute; Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA
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James MacKillop
7Peter Boris Centre for Addictions Research, McMaster University/St. Joseph’s Healthcare Hamilton, Hamilton, ON L8N 3K7, Canada; Homewood Research Institute, Guelph, ON N1E 6K9, Canada
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Abraham A. Palmer
1Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA
8Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA
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  • For correspondence: aap@ucsd.edu
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ABSTRACT

Genetic factors contribute to the risk for developing alcohol use disorder (AUD). In collaboration with the genetics company 23andMe, Inc., we performed a genome-wide association (GWAS) study of the Alcohol Use Disorder Identification Test (AUDIT), an instrument designed to screen for alcohol misuse over the past year. Our final sample consisted of 20,328 research participants of European ancestry (55.3% females; mean age = 53.8, SD = 16.1) who reported ever using alcohol. Our results showed that the ‘chip-heritability’ of AUDIT score, when treated as a continuous phenotype, was 12%. No loci reached genome-wide significance. The gene ADH1C, which has been previously implicated in AUD, was among our most significant associations (4.4 × 10−7; rs141973904). We also detected a suggestive association on chromosome 1 (2.1 × 10−7; rs182344113) near the gene KCNJ9, which has been implicated in mouse models of high ethanol drinking. Using LD score regression, we identified positive genetic correlations between AUDIT score and AUD, high alcohol consumption, and cigarette smoking. We also observed an unexpected positive genetic correlation between AUDIT and educational attainment, and additional unexpected negative correlations with BMI/obesity and attention-deficit/hyperactivity disorder (ADHD). We conclude that conducting a genetic study using data from a population unselected for AUD and responding to an online questionnaire may represent a cost-effective strategy for elucidating the etiology of AUD.

Footnotes

  • 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, Bethann S. Hromatka, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, Matthew H. McIntyre, Joanna L. Mountain, Carrie A.M. Northover, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Joyce Y. Tung, Vladimir Vacic, Catherine H. Wilson, Steven J. Pitts

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 15, 2017.
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Genome-wide association study of Alcohol Use Disorder Identification Test (AUDIT) scores in 20,328 research participants of European ancestry
Sandra Sanchez-Roige, Pierre Fontanillas, Sarah L. Elson, the 23 and Me Research Team, Joshua C. Gray, Harriet de Wit, Lea K. Davis, James MacKillop, Abraham A. Palmer
bioRxiv 147397; doi: https://doi.org/10.1101/147397
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Genome-wide association study of Alcohol Use Disorder Identification Test (AUDIT) scores in 20,328 research participants of European ancestry
Sandra Sanchez-Roige, Pierre Fontanillas, Sarah L. Elson, the 23 and Me Research Team, Joshua C. Gray, Harriet de Wit, Lea K. Davis, James MacKillop, Abraham A. Palmer
bioRxiv 147397; doi: https://doi.org/10.1101/147397

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