Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders.

Nat Neurosci
Authors
Raymond Walters
Renato Polimanti
Emma Johnson
Jeanette McClintick
Mark Adams
Amy Adkins
Fazil Aliev
Silviu-Alin Bacanu
Anthony Batzler
Sarah Bertelsen
Joanna Biernacka
Tim Bigdeli
Li-Shiun Chen
Toni-Kim Clarke
Yi-Ling Chou
Franziska Degenhardt
Anna Docherty
Alexis Edwards
Pierre Fontanillas
Jerome Foo
Louis Fox
Josef Frank
Ina Giegling
Scott Gordon
Laura Hack
Annette Hartmann
Sarah Hartz
Stefanie Heilmann-Heimbach
Stefan Herms
Colin Hodgkinson
Per Hoffmann
Jouke Hottenga
Martin Kennedy
Mervi Alanne-Kinnunen
Bettina Konte
Jari Lahti
Marius Lahti-Pulkkinen
Dongbing Lai
Lannie Ligthart
Anu Loukola
Brion Maher
Hamdi Mbarek
Andrew McIntosh
Matthew McQueen
Jacquelyn Meyers
Yuri Milaneschi
Teemu Palviainen
John Pearson
Roseann Peterson
Samuli Ripatti
Euijung Ryu
Nancy Saccone
Jessica Salvatore
Sandra Sanchez-Roige
Melanie Schwandt
Richard Sherva
Fabian Streit
Jana Strohmaier
Nathaniel Thomas
Jen-Chyong Wang
Bradley Webb
Robbee Wedow
Leah Wetherill
Amanda Wills
23andMe Research Team
Jason Boardman
Danfeng Chen
Doo-Sup Choi
William Copeland
Robert Culverhouse
Norbert Dahmen
Louisa Degenhardt
Benjamin Domingue
Sarah Elson
Mark Frye
Wolfgang Gäbel
Caroline Hayward
Marcus Ising
Margaret Keyes
Falk Kiefer
John Kramer
Samuel Kuperman
Susanne Lucae
Michael Lynskey
Wolfgang Maier
Karl Mann
Satu Männistö
Bertram Müller-Myhsok
Alison Murray
John Nurnberger
Aarno Palotie
Ulrich Preuss
Katri Räikkönen
Maureen Reynolds
Monika Ridinger
Norbert Scherbaum
Marc Schuckit
Michael Soyka
Jens Treutlein
Stephanie Witt
Norbert Wodarz
Peter Zill
Daniel Adkins
Joseph Boden
Dorret Boomsma
Laura Bierut
Sandra Brown
Kathleen Bucholz
Sven Cichon
E Jane Costello
Harriet de Wit
Nancy Diazgranados
Danielle Dick
Johan Eriksson
Lindsay Farrer
Tatiana Foroud
Nathan Gillespie
Alison Goate
David Goldman
Richard Grucza
Dana Hancock
Kathleen Harris
Andrew Heath
Victor Hesselbrock
John Hewitt
Christian Hopfer
John Horwood
William Iacono
Eric Johnson
Jaakko Kaprio
Victor Karpyak
Kenneth Kendler
Henry Kranzler
Kenneth Krauter
Paul Lichtenstein
Penelope Lind
Matt McGue
James MacKillop
Pamela Madden
Hermine Maes
Patrik Magnusson
Nicholas Martin
Sarah Medland
Grant Montgomery
Elliot Nelson
Markus Nöthen
Abraham Palmer
Nancy Pedersen
Brenda Penninx
Bernice Porjesz
John Rice
Marcella Rietschel
Brien Riley
Richard Rose
Dan Rujescu
Pei-Hong Shen
Judy Silberg
Michael Stallings
Ralph Tarter
Michael Vanyukov
Scott Vrieze
Tamara Wall
John Whitfield
Hongyu Zhao
Benjamin Neale
Joel Gelernter
Howard Edenberg
Arpana Agrawal
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.
Year of Publication
2018
Journal
Nat Neurosci
Volume
21
Issue
12
Pages
1656-1669
Date Published
2018 Dec
ISSN
1546-1726
DOI
10.1038/s41593-018-0275-1
PubMed ID
30482948
PubMed Central ID
PMC6430207
Links
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