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Nat Neurosci DOI:10.1038/s41593-018-0275-1

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

Publication TypeJournal Article
Year of Publication2018
AuthorsWalters, 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, Hottenga, JJan, 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, 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, E Costello, J, de Wit, H, Diazgranados, N, Dick, DM, Eriksson, JG, Farrer, LA, Foroud, TM, Gillespie, NA, Goate, AM, Goldman, D, Grucza, RA, Hancock, DB, Harris, KMullan, 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
Corporate Authors23andMe Research Team
JournalNat Neurosci
Volume21
Issue12
Pages1656-1669
Date Published2018 Dec
ISSN1546-1726
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.

DOI10.1038/s41593-018-0275-1
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/30482948?dopt=Abstract

Alternate JournalNat. Neurosci.
PubMed ID30482948
PubMed Central IDPMC6430207
Grant ListRC2 MH089951 / MH / NIMH NIH HHS / United States
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