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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 B. Bigdeli, Li-Shiun Chen, Toni-Kim 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 M. 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 S. 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, Richard Sherva, Fabian Streit, Jana Strohmaier, Nathaniel Thomas, Jen-Chyong Wang, Bradley T. 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 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 Müller-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 K. Bucholz, Sven Cichon, E. Jane Costello, Harriet de Wit, Nancy Diazgranados, Danielle M Dick, Johan G. Eriksson, Lindsay A. Farrer, Tatiana M. Foroud, Nathan A. Gillespie, Alison Goate, David Goldman, Richard A. Grucza, Dana B. Hancock, Kathleen Mullan Harris, Andrew C. Heath, Victor Hesselbrock, John K. Hewitt, Christian Hopfer, John Horwood, William Iacono, Eric O. Johnson, Jaakko A. 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 Maes, Patrik K. E. Magnusson, Nicholas G Martin, Sarah E. Medland, Grant W. Montgomery, Elliot C. Nelson, Markus M. Nöthen, Abraham A Palmer, Nancy L. Pedersen, Brenda Penninx, Bernice Porjesz, John P. Rice, Marcella Rietschel, Brien P. 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 M. Neale, Joel Gelernter, Howard J 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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