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Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

By Raymond K Walters, Mark J Adams, Amy E. Adkins, Fazil Aliev, Silviu-Alin Bacanu, Anthony Batzler, Sarah Bertelsen, Joanna M. Biernacka, Tim Bigdeli, Li-Shiun Chen, T-K Clarke, Yi-Ling Chou, Franziska Degenhardt, Anna R. Docherty, Pierre Fontanillas, Jerome Foo, Louis Fox, Josef Frank, Ina Giegling, Scott Gordon, Laura M Hack, Annette M Hartmann, Sarah Hartz, Stefanie Heilmann-Heimbach, Stefan Herms, Colin Hodgkinson, Per Hoffmann, Jouke- Jan Hottenga, Martin A Kennedy, Mervi Alanne-Kinnunen, Bettina Konte, Jari Lahti, Marius Lahti-Pulkkinen, lannie ligthart, Anu-Maria Loukola, Brion Maher, Hamdi Mbarek, Andrew M McIntosh, Matthew B McQueen, Yuri Milaneschi, Teemu Palviainen, John F. Pearson, Roseann E Peterson, Renato Polimanti, Samuli Ripatti, Euijung Ryu, Nancy L Saccone, Jessica E. Salvatore, Sandra Sanchez-Roige, Melanie Schwandt, Joel Gelernter, Fabian Streit, Jana Strohmaier, Nathaniel Thomas, Jen-Chyong Wang, Bradley Todd Webb, Robbee Wedow, Leah Wetherill, Amanda G. Wills, 23andMe Research Team, Jason D. Boardman, Danfeng Chen, Doo-Sup Choi, William E. Copeland, Robert C. Culverhouse, Norbert Dahmen, Louisa Degenhardt, Benjamin W Domingue, Sarah L Elson, Mark A. Frye, Wolfgang Gäbel, Marcus Ising, Emma C Johnson, Margaret Keyes, Falk Kiefer, John R Kramer, Samuel Kuperman, Susanne Lucae, Michael Lynskey, Wolfgang Maier, Karl Mann, Satu Männistö, Jeanette Nance McClintick, Jacquelyn L. Meyers, Bertram Mueller-Myhsok, John I. Nurnberger, Aarno Palotie, Ulrich Preuss, Katri Räikkönen, Maureen D. Reynolds, Monika Ridinger, Norbert Scherbaum, Marc Shuckit, Michael Soyka, Jens Treutlein, Stephanie H Witt, Norbert Wodarz, Peter Zill, Daniel E Adkins, Joseph M. Boden, Dorret I Boomsma, Laura J Bierut, Sandra A. Brown, Kathleen Bucholz, Sven Cichon, E. Jane Costello, Harriet de Wit, Nancy Diazgranados, Danielle M Dick, Johan G. Eriksson, Lindsay Farrer, Tatiana Foroud, Nathan A Gillespie, Alison Goate, David Goldman, Richard A. Grucza, Dana B Hancock, Kathleen Mullan Harris, Andrew C. Heath, Victor Hesselbrock, John Hewitt, Christian Hopfer, John Horwood, William Iacono, Eric O Johnson, Jaakko Kaprio, Victor Karpyak, Kenneth S Kendler, Henry R. Kranzler, Kenneth Krauter, Paul Lichtenstein, Penelope A. Lind, Matt McGue, James MacKillop, Pamela A.F. Madden, Hermine H Maes, Patrik KE Magnusson, Nicholas G Martin, Sarah. Medland, Grant W Montgomery, Elliot C Nelson, Markus M Nöthen, Abraham A. Palmer, Nancy L. Pedersen, Brenda WJH Penninx, Bernice Porjesz, John P. Rice, Marcella Rietschel, Brien Riley, Richard Rose, Dan Rujescu, Pei-Hong Shen, Judy Silberg, Michael C. Stallings, Ralph E. Tarter, Michael M. Vanyukov, Scott Vrieze, Tamara L. Wall, John B. Whitfield, Hongyu Zhao, Benjamin Neale, Joel Gelernter, Howard Edenberg, Arpana Agrawal

Posted 10 Mar 2018
bioRxiv DOI: 10.1101/257311 (published DOI: 10.1038/s41593-018-0275-1)

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest GWAS to date of DSM-IV diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case/control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, N = 46,568; African; N = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; p = 9.8E-13) and African ancestries (rs2066702; p = 2.2E-9). Significant genetic correlations were observed with schizophrenia, ADHD, depression, and use of cigarettes and cannabis. There was only modest genetic correlation with alcohol consumption and inconsistent associations with problem drinking. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and non-pathological drinking behaviors.

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