Transancestral GWAS of Alcohol Dependence Reveals Common Genetic Underpinnings with Psychiatric Disorders

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Walters, Raymond K.; Polimanti, Renato; Johnson, Emma C.; McClintick, Jeanette N.; Adams, Mark J.; Adkins, Amy E.; Aliev, Fazil; Bacanu, Silviu-Alin; Batzler, Anthony; & Bertelsen, Sarah, et al. (2018). Transancestral GWAS of Alcohol Dependence Reveals Common Genetic Underpinnings with Psychiatric Disorders. Nature Neuroscience, 21(12), 1656-1669. PMCID: PMC6430207

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 x 10(-13)) and African ancestries (rs2066702; P = 2.2 x 10(-9)). 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.

URL

http://dx.doi.org/10.1038/s41593-018-0275-1

Reference Type

Journal Article

Year Published

2018

Journal Title

Nature Neuroscience

Author(s)

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

PMCID

PMC6430207

ORCiD

Harris, KM - 0000-0001-9757-1026