Journal article
Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders
Nature neuroscience, Vol.21(12), pp.1656-1669
12/2018
DOI: 10.1038/s41593-018-0275-1
PMCID: PMC6430207
PMID: 30482948
Abstract
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 genome-wide association study 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 = 9.8 × 10
) and African ancestries (rs2066702; P = 2.2 × 10
). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.
Details
- Title: Subtitle
- Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders
- Creators
- Raymond K Walters - Broad InstituteRenato Polimanti - Yale UniversityEmma C Johnson - Washington University in St. LouisJeanette N McClintick - Indiana UniversityMark J Adams - University of EdinburghAmy E Adkins - Virginia Commonwealth UniversityFazil Aliev - Virginia Commonwealth UniversitySilviu-Alin Bacanu - Virginia Commonwealth UniversityAnthony Batzler - Mayo ClinicSarah Bertelsen - Icahn School of Medicine at Mount SinaiJoanna M Biernacka - Mayo ClinicTim B Bigdeli - SUNY Downstate Health Sciences UniversityLi-Shiun Chen - Washington University in St. LouisToni-Kim Clarke - University of EdinburghYi-Ling Chou - Washington University in St. LouisFranziska Degenhardt - University of BonnAnna R Docherty - University of UtahAlexis C Edwards - Virginia Commonwealth UniversityPierre Fontanillas - 23andMe (United States)Jerome C Foo - Heidelberg UniversityLouis Fox - Washington University in St. LouisJosef Frank - Heidelberg UniversityIna Giegling - Martin Luther University Halle-WittenbergScott Gordon - QIMR Berghofer Medical Research InstituteLaura M Hack - Emory UniversityAnnette M Hartmann - Martin Luther University Halle-WittenbergSarah M Hartz - Washington University in St. LouisStefanie Heilmann-Heimbach - University of BonnStefan Herms - University of BonnColin Hodgkinson - National Institutes of HealthPer Hoffmann - University of BonnJouke Jan Hottenga - Vrije Universiteit AmsterdamMartin A Kennedy - University of OtagoMervi Alanne-Kinnunen - University of HelsinkiBettina Konte - Martin Luther University Halle-WittenbergJari Lahti - University of HelsinkiMarius Lahti-Pulkkinen - University of HelsinkiDongbing Lai - Indiana UniversityLannie Ligthart - Vrije Universiteit AmsterdamAnu Loukola - University of HelsinkiBrion S Maher - Johns Hopkins UniversityHamdi Mbarek - Vrije Universiteit AmsterdamAndrew M McIntosh - University of EdinburghMatthew B McQueen - University of Colorado BoulderJacquelyn L Meyers - SUNY Downstate Health Sciences UniversityYuri Milaneschi - Public Health Research InstituteTeemu Palviainen - University of HelsinkiJohn F Pearson - University of OtagoRoseann E Peterson - Virginia Commonwealth UniversitySamuli Ripatti - University of HelsinkiEuijung Ryu - Mayo ClinicNancy L Saccone - Washington University in St. LouisJessica E Salvatore - Virginia Commonwealth UniversitySandra Sanchez-Roige - University of California San DiegoMelanie Schwandt - National Institutes of HealthRichard Sherva - Boston UniversityFabian Streit - Heidelberg UniversityJana Strohmaier - Heidelberg UniversityNathaniel Thomas - Virginia Commonwealth UniversityJen-Chyong Wang - Icahn School of Medicine at Mount SinaiBradley T Webb - Virginia Commonwealth UniversityRobbee Wedow - Harvard UniversityLeah Wetherill - Indiana UniversityAmanda G Wills - University of Colorado DenverJason D Boardman - University of Colorado BoulderDanfeng Chen - Broad InstituteDoo-Sup Choi - Mayo ClinicWilliam E Copeland - Duke UniversityRobert C Culverhouse - Washington University in St. LouisNorbert Dahmen - Johannes Gutenberg University MainzLouisa Degenhardt - National Drug and Alcohol Research CentreBenjamin W Domingue - Stanford UniversitySarah L Elson - 23andMe (United States)Mark A Frye - Mayo ClinicWolfgang Gäbel - Heinrich Heine University DüsseldorfCaroline Hayward - University of EdinburghMarcus Ising - Max Planck SocietyMargaret Keyes - University of MinnesotaFalk Kiefer - Heidelberg UniversityJohn Kramer - University of IowaSamuel Kuperman - University of IowaSusanne Lucae - Max Planck SocietyMichael T Lynskey - King's College LondonWolfgang Maier - University of BonnKarl Mann - Heidelberg UniversitySatu Männistö - Institute for Health and Welfare, Helsinki, FinlandBertram Müller-Myhsok - Max Planck SocietyAlison D Murray - University of AberdeenJohn I Nurnberger - Indiana UniversityAarno Palotie - Massachusetts General HospitalUlrich Preuss - Martin Luther University Halle-WittenbergKatri Räikkönen - University of HelsinkiMaureen D Reynolds - University of PittsburghMonika Ridinger - University of RegensburgNorbert Scherbaum - University of Duisburg-EssenMarc A Schuckit - University of California San DiegoMichael Soyka - Ludwig-Maximilians-Universität MünchenJens Treutlein - Heidelberg UniversityStephanie Witt - Heidelberg UniversityNorbert Wodarz - University of RegensburgPeter Zill - Ludwig-Maximilians-Universität MünchenDaniel E Adkins - University of UtahJoseph M Boden - University of OtagoDorret I Boomsma - Vrije Universiteit AmsterdamLaura J Bierut - Washington University in St. LouisSandra A Brown - University of California San DiegoKathleen K Bucholz - Washington University in St. LouisSven Cichon - University Hospital of BaselE Jane Costello - Duke UniversityHarriet de Wit - National Institutes of HealthNancy Diazgranados - National Institutes of HealthDanielle M Dick - Virginia Commonwealth UniversityJohan G Eriksson - National Institutes of HealthLindsay A Farrer - Boston UniversityTatiana M Foroud - Indiana UniversityNathan A Gillespie - Virginia Commonwealth UniversityAlison M Goate - Icahn School of Medicine at Mount SinaiDavid Goldman - National Institutes of HealthRichard A Grucza - Washington University in St. LouisDana B Hancock - Research Triangle Park FoundationKathleen Mullan Harris - University of North Carolina at Chapel HillAndrew C Heath - Washington University in St. LouisVictor Hesselbrock - University of ConnecticutJohn K Hewitt - University of Colorado BoulderChristian J Hopfer - University of Colorado DenverJohn Horwood - University of OtagoWilliam Iacono - University of MinnesotaEric O Johnson - Research Triangle Park FoundationJaakko A Kaprio - University of HelsinkiVictor M Karpyak - Mayo ClinicKenneth S Kendler - Virginia Commonwealth UniversityHenry R Kranzler - University of PennsylvaniaKenneth Krauter - University of Colorado BoulderPaul Lichtenstein - Department of Medical Epidemiology and Biostatistics, Karolinska Instituet, Stockholm, SwedenPenelope A Lind - QIMR Berghofer Medical Research InstituteMatt McGue - University of MinnesotaJames MacKillop - St. Joseph’s Healthcare HamiltonPamela A F Madden - Washington University in St. LouisHermine H Maes - Virginia Commonwealth UniversityPatrik Magnusson - Department of Medical Epidemiology and Biostatistics, Karolinska Instituet, Stockholm, SwedenNicholas G Martin - QIMR Berghofer Medical Research InstituteSarah E Medland - QIMR Berghofer Medical Research InstituteGrant W Montgomery - The University of QueenslandElliot C Nelson - Washington University in St. LouisMarkus M Nöthen - University Hospital BonnAbraham A Palmer - University of California San DiegoNancy L Pedersen - Department of Medical Epidemiology and Biostatistics, Karolinska Instituet, Stockholm, SwedenBrenda W J H Penninx - Public Health Research InstituteBernice Porjesz - SUNY Downstate Health Sciences UniversityJohn P Rice - Washington University in St. LouisMarcella Rietschel - Heidelberg UniversityBrien P Riley - Virginia Commonwealth UniversityRichard Rose - Indiana UniversityDan Rujescu - Martin Luther University Halle-WittenbergPei-Hong Shen - National Institutes of HealthJudy Silberg - Virginia Commonwealth UniversityMichael C Stallings - University of Colorado BoulderRalph E Tarter - University of PittsburghMichael M Vanyukov - University of PittsburghScott Vrieze - University of MinnesotaTamara L Wall - University of California San DiegoJohn B Whitfield - QIMR Berghofer Medical Research InstituteHongyu Zhao - Yale UniversityBenjamin M Neale - Broad InstituteJoel Gelernter - Yale UniversityHoward J Edenberg - Indiana UniversityArpana Agrawal - Washington University in St. Louis23andMe Research Team
- Resource Type
- Journal article
- Publication Details
- Nature neuroscience, Vol.21(12), pp.1656-1669
- DOI
- 10.1038/s41593-018-0275-1
- PMID
- 30482948
- PMCID
- PMC6430207
- NLM abbreviation
- Nat Neurosci
- ISSN
- 1097-6256
- eISSN
- 1546-1726
- Grant note
- P2C HD066613 / NICHD NIH HHS R01 DA012854 / NIDA NIH HHS R01 AA013321 / NIAAA NIH HHS R37 DA005147 / NIDA NIH HHS R01 DA036628 / NIDA NIH HHS R56 DA012854 / NIDA NIH HHS K08 DA032680 / NIDA NIH HHS HHSN268200782096C / NHGRI NIH HHS R01 DA024417 / NIDA NIH HHS K01 MH113848 / NIMH NIH HHS R37 AA012502 / NIAAA NIH HHS R01 MH063970 / NIMH NIH HHS R01 HD060726 / NICHD NIH HHS R01 MH100549 / NIMH NIH HHS K05 AA017688 / NIAAA NIH HHS R01 DA046436 / NIDA NIH HHS R01 MH107649 / NIMH NIH HHS R01 DA013240 / NIDA NIH HHS RC2 MH089995 / NIMH NIH HHS R37 AA011408 / NIAAA NIH HHS P50 AA011998 / NIAAA NIH HHS P50 DA005605 / NIDA NIH HHS R01 DA036216 / NIDA NIH HHS K08 DA019951 / NIDA NIH HHS R01 DA038076 / NIDA NIH HHS R37 AA007728 / NIAAA NIH HHS R01 AA009203 / NIAAA NIH HHS R01 DA021913 / NIDA NIH HHS P20 AA017828 / NIAAA NIH HHS Wellcome Trust R01 DA021905 / NIDA NIH HHS R01 DA042755 / NIDA NIH HHS R00 DA023549 / NIDA NIH HHS R01 HD073342 / NICHD NIH HHS P50 DA037844 / NIDA NIH HHS R01 DA019963 / NIDA NIH HHS R01 DA037904 / NIDA NIH HHS N01HG65403 / NHGRI NIH HHS R01 DA042620 / NIDA NIH HHS K01 MH109765 / NIMH NIH HHS R01 DA005147 / NIDA NIH HHS R01 AA011408 / NIAAA NIH HHS R01 DA018432 / NIDA NIH HHS P20 AA017830 / NIAAA NIH HHS R01 DA036583 / NIDA NIH HHS R01 MH081802 / NIMH NIH HHS R01 DA016977 / NIDA NIH HHS R01 HD042157 / NICHD NIH HHS U01 HG004422 / NHGRI NIH HHS U10 AA008401 / NIAAA NIH HHS U01 HG004438 / NHGRI NIH HHS R01 AA011330 / NIAAA NIH HHS U01 DA024417 / NIDA NIH HHS R01 MH063671 / NIMH NIH HHS R21 DA040177 / NIDA NIH HHS R01 AA012502 / NIAAA NIH HHS U01 MH094432 / NIMH NIH HHS R01 AA017444 / NIAAA NIH HHS R01 DA024413 / NIDA NIH HHS U01 MH109536 / NIMH NIH HHS P60 DA011015 / NIDA NIH HHS K01 DA037914 / NIDA NIH HHS R01 AA007535 / NIAAA NIH HHS R01 DA013423 / NIDA NIH HHS K24 DA032555 / NIDA NIH HHS R37 AA009367 / NIAAA NIH HHS R01 HG008983 / NHGRI NIH HHS P01 HD031921 / NICHD NIH HHS R01 DA012845 / NIDA NIH HHS K05 AA000145 / NIAAA NIH HHS U01 DA024413 / NIDA NIH HHS R01 DA017305 / NIDA NIH HHS R01 DA036523 / NIDA NIH HHS P2C HD050924 / NICHD NIH HHS UL1 TR000135 / NCATS NIH HHS R01 MH048085 / NIMH NIH HHS U24 MH068457 / NIMH NIH HHS R21 DA041883 / NIDA NIH HHS R33 DA041883 / NIDA NIH HHS R25 DA027995 / NIDA NIH HHS R01 DA039408 / NIDA NIH HHS K01 MH093731 / NIMH NIH HHS R01 DA025109 / NIDA NIH HHS U01 DK066134 / NIDDK NIH HHS U01 MH109539 / NIMH NIH HHS R01 DA002812 / NIDA NIH HHS K01 AA021399 / NIAAA NIH HHS P50 AA022537 / NIAAA NIH HHS R21 DA043735 / NIDA NIH HHS R01 MH083094 / NIMH NIH HHS R01 DA012690 / NIDA NIH HHS U01 MH109532 / NIMH NIH HHS K02 DA032573 / NIDA NIH HHS R01 DA035804 / NIDA NIH HHS RC2 DA028909 / NIDA NIH HHS RC2 MH089951 / NIMH NIH HHS R01 AA015416 / NIAAA NIH HHS P30 DA023026 / NIDA NIH HHS R01 MH068521 / NIMH NIH HHS R01 MH077874 / NIMH NIH HHS T32 AA007464 / NIAAA NIH HHS K02 AA018755 / NIAAA NIH HHS R01 AA009367 / NIAAA NIH HHS R01 DA019157 / NIDA NIH HHS R01 AA013320 / NIAAA NIH HHS R01 DA011301 / NIDA NIH HHS K01 AA024152 / NIAAA NIH HHS R01 DA012849 / NIDA NIH HHS R01 HD093651 / NICHD NIH HHS R01 AA007728 / NIAAA NIH HHS R01 MH066140 / NIMH NIH HHS R21 AA022717 / NIAAA NIH HHS MR/K026992/1 / Medical Research Council R21 AA025214 / NIAAA NIH HHS P01 CA089392 / NCI NIH HHS
- Language
- English
- Date published
- 12/2018
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293657702771
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