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

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

Nat Neurosci 2018 12 26;21(12):1656-1669. Epub 2018 Nov 26.

Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.

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.

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http://dx.doi.org/10.1038/s41593-018-0275-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430207PMC
December 2018
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