Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders
Authors: Walters Raymond K. , Adams Mark J. , Adkins Amy E. , Aliev Fazil , Bacanu Silviu-Alin , Batzler Anthony , Bertelsen Sarah , Biernacka Joanna , Bigdeli Tim B. , Chen Li-Shiun , Clarke Toni-Kim , Chou Yi-Ling , Degenhardt Franziska , Docherty Anna R. , Fontanillas Pierre , Foo Jerome , Fox Louis , Frank Josef , Giegling Ina , Gordon Scott , Hack Laura M. , Hartmann Annette M. , Hartz Sarah M. , Heilmann-Heimbach Stefanie , Herms Stefan , Hodgkinson Colin , Hoffmann Per , Hottenga Jouke-Jan , Kennedy Martin A. , Alanne-Kinnunen Mervi , Konte Bettina , Lahti Jari , Lahti-Pulkkinen Marius , Ligthart Lannie , Loukola Anu-Maria , Maher Brion S. , Mbarek Hamdi , McIntosh Andrew M. , McQueen Matthew B. , Milaneschi Yuri , Palviainen Teemu , Pearson John F. , Peterson Roseann E. , Polimanti Renato , Ripatti Samuli , Ryu Euijung , Saccone Nancy L. , Salvatore Jessica E. , Sanchez-Roige Sandra , Schwandt Melanie , Sherva Richard , Streit Fabian , Strohmaier Jana , Thomas Nathaniel , Wang Jen-Chyong , Webb Bradley T. , Wedow Robbee , Wetherill Leah , Wills Amanda G. ,   23andMe Research Team, Boardman Jason D. , Chen Danfeng , Choi Doo-Sup , Copeland William E. , Culverhouse Robert C. , Dahmen Norbert , Degenhardt Louisa , Domingue Benjamin W. , Elson Sarah L. , Frye Mark , Gäbel Wolfgang , Ising Marcus , Johnson Emma C. , Keyes Margaret , Kiefer Falk , Kramer John , Kuperman Samuel , Lucae Susanne , Lynskey Michael T. , Maier Wolfgang , Mann Karl , Männistö Satu , McClintick Jeanette Nance , Meyers Jacquelyn L. , Müller-Myhsok Bertram , Nurnberger John I. , Palotie Aarno , Preuss Ulrich , Räikkönen Katri , Reynolds Maureen D. , Ridinger Monika , Scherbaum Norbert , Shuckit Marc , Soyka Michael , Treutlein Jens , Witt Stephanie , Wodarz Norbert , Zill Peter , Adkins Daniel E. , Boden Joseph M. , Boomsma Dorret , Bierut Laura J , Brown Sandra A. , Bucholz Kathleen K. , Cichon Sven , Costello E. Jane , de Wit Harriet , Diazgranados Nancy , Dick Danielle M. , Eriksson Johan G. , Farrer Lindsay A. , Foroud Tatiana M. , Gillespie Nathan A. , Goate Alison A. , Goldman David , Grucza Richard A. , Hancock Dana B. , Harris Kathleen Mullan , Heath Andrew C. , Hesselbrock Victor , Hewitt John K. , Hopfer Christian , Horwood John , Iacono William , Johnson Eric O. , Kaprio Jaakko A. , Karpyak Victor , Kendler Kenneth S. , Kranzler Henry R. , Krauter Kenneth , Lichtenstein Paul , Lind Penelope A. , McGue Matt , MacKillop James , Madden Pamela A.F. , Maes Hermine , Magnusson Patrik , Martin Nicholas G. , Medland Sarah E. , Montgomery Grant W. , Nelson Elliot C. , Nöthen Markus , Palmer Abraham A. , Pedersen Nancy L. , Penninx Brenda W.J.H. , Porjesz Bernice , Rice John P. , Rietschel Marcella , Riley Brien P. , Rose Richard , Rujescu Dan , Shen Pei-Hong , Silberg Judy , Stallings Michael C. , Tarter Ralph E. , Vanyukov Michael M. , Vrieze Scott , Wall Tamara L. , Whitfield John B. , Zhao Hongyu , Neale Benjamin M. , Gelernter Joel , Edenberg Howard J. , Agrawal Arpana 
Published: March 2018

AbstractLiability 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.