6533b7dbfe1ef96bd1270cf8

RESEARCH PRODUCT

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

Raymond K. WaltersMark J. AdamsAmy E. AdkinsFazil AlievSilviu-alin BacanuAnthony BatzlerSarah BertelsenJoanna BiernackaTim B. BigdeliLi-shiun ChenToni-kim ClarkeYi-ling ChouFranziska DegenhardtAnna R. DochertyPierre FontanillasJerome FooLouis FoxJosef FrankIna GieglingScott GordonLaura M. HackAnnette M. HartmannSarah M. HartzStefanie Heilmann-heimbachStefan HermsColin HodgkinsonPer HoffmannJouke-jan HottengaMartin A. KennedyMervi Alanne-kinnunenBettina KonteJari LahtiMarius Lahti-pulkkinenLannie LigthartAnu-maria LoukolaBrion S. MaherHamdi MbarekAndrew M. McintoshMatthew B. McqueenYuri MilaneschiTeemu PalviainenJohn F. PearsonRoseann E. PetersonRenato PolimantiSamuli RipattiEuijung RyuNancy L. SacconeJessica E. SalvatoreSandra Sanchez-roigeMelanie SchwandtRichard ShervaFabian StreitJana StrohmaierNathaniel ThomasJen-chyong WangBradley T. WebbRobbee WedowLeah WetherillAmanda G. WillsJason D. BoardmanDanfeng ChenDoo-sup ChoiWilliam E. CopelandRobert C. CulverhouseNorbert DahmenLouisa DegenhardtBenjamin W. DomingueSarah L. ElsonMark FryeWolfgang GäbelMarcus IsingEmma C. JohnsonMargaret KeyesFalk KieferJohn KramerSamuel KupermanSusanne LucaeMichael T. LynskeyWolfgang MaierKarl MannSatu MännistöJeanette Nance McclintickJacquelyn L. MeyersBertram Müller-myhsokJohn I. NurnbergerAarno PalotieUlrich PreussKatri RäikkönenMaureen D. ReynoldsMonika RidingerNorbert ScherbaumMarc ShuckitMichael SoykaJens TreutleinStephanie WittNorbert WodarzPeter ZillDaniel E. AdkinsJoseph M. BodenDorret BoomsmaLaura J BierutSandra A. BrownKathleen K. BucholzSven CichonE. Jane CostelloHarriet De WitNancy DiazgranadosDanielle M. DickJohan G. ErikssonLindsay A. FarrerTatiana M. ForoudNathan A. GillespieAlison A. GoateDavid GoldmanRichard A. GruczaDana B. HancockKathleen Mullan HarrisAndrew C. HeathVictor HesselbrockJohn K. HewittChristian HopferJohn HorwoodWilliam IaconoEric O. JohnsonJaakko A. KaprioVictor KarpyakKenneth S. KendlerHenry R. KranzlerKenneth KrauterPaul LichtensteinPenelope A. LindMatt McgueJames MackillopPamela A.f. MaddenHermine MaesPatrik MagnussonNicholas G. MartinSarah E. MedlandGrant W. MontgomeryElliot C. NelsonMarkus NöthenAbraham A. PalmerNancy L. PedersenBrenda W.j.h. PenninxBernice PorjeszJohn P. RiceMarcella RietschelBrien P. RileyRichard RoseDan RujescuPei-hong ShenJudy SilbergMichael C. StallingsRalph E. TarterMichael M. VanyukovScott VriezeTamara L. WallJohn B. WhitfieldHongyu ZhaoBenjamin M. NealeJoel GelernterHoward J. EdenbergArpana Agrawal

subject

0303 health sciencesmedicine.medical_specialtybiologyGenetic genealogyAlcohol dependenceADH1BGenome-wide association studybiology.organism_classificationmedicine.diseaseGenetic correlation3. Good health03 medical and health sciences0302 clinical medicineSchizophreniamedicineCannabisPsychiatry030217 neurology & neurosurgeryDepression (differential diagnoses)030304 developmental biology

description

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.

yearjournalcountryeditionlanguage
2018-03-10
10.1101/257311http://dx.doi.org/10.1101/257311