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

Author:

Walters Raymond K.,Adams Mark J.ORCID,Adkins Amy E.ORCID,Aliev FazilORCID,Bacanu Silviu-AlinORCID,Batzler AnthonyORCID,Bertelsen SarahORCID,Biernacka JoannaORCID,Bigdeli Tim B.ORCID,Chen Li-ShiunORCID,Clarke Toni-KimORCID,Chou Yi-Ling,Degenhardt FranziskaORCID,Docherty Anna R.ORCID,Fontanillas Pierre,Foo Jerome,Fox LouisORCID,Frank JosefORCID,Giegling InaORCID,Gordon Scott,Hack Laura M.ORCID,Hartmann Annette M.ORCID,Hartz Sarah M.ORCID,Heilmann-Heimbach StefanieORCID,Herms StefanORCID,Hodgkinson ColinORCID,Hoffmann PerORCID,Hottenga Jouke-JanORCID,Kennedy Martin A.ORCID,Alanne-Kinnunen Mervi,Konte BettinaORCID,Lahti JariORCID,Lahti-Pulkkinen MariusORCID,Ligthart LannieORCID,Loukola Anu-MariaORCID,Maher Brion S.ORCID,Mbarek HamdiORCID,McIntosh Andrew M.ORCID,McQueen Matthew B.ORCID,Milaneschi YuriORCID,Palviainen TeemuORCID,Pearson John F.ORCID,Peterson Roseann E.ORCID,Polimanti RenatoORCID,Ripatti SamuliORCID,Ryu EuijungORCID,Saccone Nancy L.ORCID,Salvatore Jessica E.ORCID,Sanchez-Roige Sandra,Schwandt Melanie,Sherva RichardORCID,Streit FabianORCID,Strohmaier JanaORCID,Thomas NathanielORCID,Wang Jen-ChyongORCID,Webb Bradley T.ORCID,Wedow RobbeeORCID,Wetherill LeahORCID,Wills Amanda G.ORCID,Boardman Jason D.ORCID,Chen Danfeng,Choi Doo-SupORCID,Copeland William E.ORCID,Culverhouse Robert C.ORCID,Dahmen Norbert,Degenhardt LouisaORCID,Domingue Benjamin W.ORCID,Elson Sarah L.,Frye MarkORCID,Gäbel Wolfgang,Ising MarcusORCID,Johnson Emma C.,Keyes Margaret,Kiefer FalkORCID,Kramer JohnORCID,Kuperman SamuelORCID,Lucae SusanneORCID,Lynskey Michael T.ORCID,Maier WolfgangORCID,Mann KarlORCID,Männistö Satu,McClintick Jeanette NanceORCID,Meyers Jacquelyn L.ORCID,Müller-Myhsok BertramORCID,Nurnberger John I.ORCID,Palotie AarnoORCID,Preuss Ulrich,Räikkönen KatriORCID,Reynolds Maureen D.ORCID,Ridinger MonikaORCID,Scherbaum NorbertORCID,Shuckit Marc,Soyka MichaelORCID,Treutlein JensORCID,Witt StephanieORCID,Wodarz NorbertORCID,Zill PeterORCID,Adkins Daniel E.ORCID,Boden Joseph M.ORCID,Boomsma DorretORCID,Bierut Laura JORCID,Brown Sandra A.ORCID,Bucholz Kathleen K.ORCID,Cichon SvenORCID,Costello E. JaneORCID,de Wit Harriet,Diazgranados Nancy,Dick Danielle M.ORCID,Eriksson Johan G.ORCID,Farrer Lindsay A.ORCID,Foroud Tatiana M.ORCID,Gillespie Nathan A.ORCID,Goate Alison A.ORCID,Goldman DavidORCID,Grucza Richard A.ORCID,Hancock Dana B.ORCID,Harris Kathleen MullanORCID,Heath Andrew C.ORCID,Hesselbrock VictorORCID,Hewitt John K.ORCID,Hopfer ChristianORCID,Horwood JohnORCID,Iacono William,Johnson Eric O.ORCID,Kaprio Jaakko A.ORCID,Karpyak VictorORCID,Kendler Kenneth S.ORCID,Kranzler Henry R.ORCID,Krauter KennethORCID,Lichtenstein PaulORCID,Lind Penelope A.ORCID,McGue Matt,MacKillop JamesORCID,Madden Pamela A.F.ORCID,Maes HermineORCID,Magnusson PatrikORCID,Martin Nicholas G.ORCID,Medland Sarah E.ORCID,Montgomery Grant W.ORCID,Nelson Elliot C.ORCID,Nöthen MarkusORCID,Palmer Abraham A.ORCID,Pedersen Nancy L.ORCID,Penninx Brenda W.J.H.ORCID,Porjesz BerniceORCID,Rice John P.ORCID,Rietschel MarcellaORCID,Riley Brien P.ORCID,Rose Richard,Rujescu DanORCID,Shen Pei-Hong,Silberg Judy,Stallings Michael C.ORCID,Tarter Ralph E.ORCID,Vanyukov Michael M.ORCID,Vrieze Scott,Wall Tamara L.ORCID,Whitfield John B.ORCID,Zhao HongyuORCID,Neale Benjamin M.ORCID,Gelernter JoelORCID,Edenberg Howard J.ORCID,Agrawal ArpanaORCID,

Abstract

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.

Publisher

Cold Spring Harbor Laboratory

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