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

Journal Article (Journal Article)

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

Full Text

Duke Authors

Cited Authors

  • Walters, RK; Polimanti, R; Johnson, EC; McClintick, JN; Adams, MJ; Adkins, AE; Aliev, F; Bacanu, S-A; Batzler, A; Bertelsen, S; Biernacka, JM; Bigdeli, TB; Chen, L-S; Clarke, T-K; Chou, Y-L; Degenhardt, F; Docherty, AR; Edwards, AC; Fontanillas, P; Foo, JC; Fox, L; Frank, J; Giegling, I; Gordon, S; Hack, LM; Hartmann, AM; Hartz, SM; Heilmann-Heimbach, S; Herms, S; Hodgkinson, C; Hoffmann, P; Jan Hottenga, J; Kennedy, MA; Alanne-Kinnunen, M; Konte, B; Lahti, J; Lahti-Pulkkinen, M; Lai, D; Ligthart, L; Loukola, A; Maher, BS; Mbarek, H; McIntosh, AM; McQueen, MB; Meyers, JL; Milaneschi, Y; Palviainen, T; Pearson, JF; Peterson, RE; Ripatti, S; Ryu, E; Saccone, NL; Salvatore, JE; Sanchez-Roige, S; Schwandt, M; Sherva, R; Streit, F; Strohmaier, J; Thomas, N; Wang, J-C; Webb, BT; Wedow, R; Wetherill, L; Wills, AG; 23andMe Research Team, ; Boardman, JD; Chen, D; Choi, D-S; Copeland, WE; Culverhouse, RC; Dahmen, N; Degenhardt, L; Domingue, BW; Elson, SL; Frye, MA; Gäbel, W; Hayward, C; Ising, M; Keyes, M; Kiefer, F; Kramer, J; Kuperman, S; Lucae, S; Lynskey, MT; Maier, W; Mann, K; Männistö, S; Müller-Myhsok, B; Murray, AD; Nurnberger, JI; Palotie, A; Preuss, U; Räikkönen, K; Reynolds, MD; Ridinger, M; Scherbaum, N; Schuckit, MA; Soyka, M; Treutlein, J; Witt, S; Wodarz, N; Zill, P; Adkins, DE; Boden, JM; Boomsma, DI; Bierut, LJ; Brown, SA; Bucholz, KK; Cichon, S; Costello, EJ; de Wit, H; Diazgranados, N; Dick, DM; Eriksson, JG; Farrer, LA; Foroud, TM; Gillespie, NA; Goate, AM; Goldman, D; Grucza, RA; Hancock, DB; Harris, KM; Heath, AC; Hesselbrock, V; Hewitt, JK; Hopfer, CJ; Horwood, J; Iacono, W; Johnson, EO; Kaprio, JA; Karpyak, VM; Kendler, KS; Kranzler, HR; Krauter, K; Lichtenstein, P; Lind, PA; McGue, M; MacKillop, J; Madden, PAF; Maes, HH; Magnusson, P; Martin, NG; Medland, SE; Montgomery, GW; Nelson, EC; Nöthen, MM; Palmer, AA; Pedersen, NL; Penninx, BWJH; Porjesz, B; Rice, JP; Rietschel, M; Riley, BP; Rose, R; Rujescu, D; Shen, P-H; Silberg, J; Stallings, MC; Tarter, RE; Vanyukov, MM; Vrieze, S; Wall, TL; Whitfield, JB; Zhao, H; Neale, BM; Gelernter, J; Edenberg, HJ; Agrawal, A

Published Date

  • December 2018

Published In

Volume / Issue

  • 21 / 12

Start / End Page

  • 1656 - 1669

PubMed ID

  • 30482948

Pubmed Central ID

  • 30482948

Electronic International Standard Serial Number (EISSN)

  • 1546-1726

Digital Object Identifier (DOI)

  • 10.1038/s41593-018-0275-1

Language

  • eng

Conference Location

  • United States