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

被引：405

作者：

Walters, Raymond K. ^{[1
,2
,3
]}

Polimanti, Renato ^{[4
,5
]}

Johnson, Emma C. ^{[6
]}

McClintick, Jeanette N. ^{[7
]}

Adams, Mark J. ^{[8
]}

Adkins, Amy E. ^{[9
,10
]}

Aliev, Fazil ^{[11
]}

Bacanu, Silviu-Alin ^{[12
]}

Batzler, Anthony ^{[13
]}

Bertelsen, Sarah ^{[14
]}

Biernacka, Joanna M. ^{[15
,16
]}

Bigdeli, Tim B. ^{[17
]}

Chen, Li-Shiun ^{[6
]}

Clarke, Toni-Kim ^{[8
]}

Chou, Yi-Ling ^{[6
]}

Degenhardt, Franziska ^{[18
,19
]}

Docherty, Anna R. ^{[20
]}

Edwards, Alexis C. ^{[21
]}

Fontanillas, Pierre ^{[22
]}

Foo, Jerome C. ^{[23
]}

Fox, Louis ^{[6
]}

Frank, Josef ^{[23
]}

Giegling, Ina ^{[24
]}

Gordon, Scott ^{[25
]}

Hack, Laura M. ^{[26
]}

Hartmann, Annette M. ^{[24
]}

Hartz, Sarah M. ^{[6
]}

Heilmann-Heimbach, Stefanie ^{[18
,19
]}

Herms, Stefan ^{[18
,19
,27
]}

Hodgkinson, Colin ^{[28
]}

Hoffmann, Per ^{[18
,19
,27
]}

Hottenga, Jouke Jan ^{[29
]}

Kennedy, Martin A. ^{[30
]}

Alanne-Kinnunen, Mervi ^{[31
]}

Konte, Bettina ^{[24
]}

Lahti, Jari ^{[32
,33
]}

Lahti-Pulkkinen, Marius ^{[33
]}

Lai, Dongbing ^{[34
]}

Ligthart, Lannie ^{[29
]}

Loukola, Anu ^{[31
]}

Maher, Brion S. ^{[35
]}

Mbarek, Hamdi ^{[29
]}

McIntosh, Andrew M. ^{[36
]}

McQueen, Matthew B. ^{[37
]}

Meyers, Jacquelyn L. ^{[38
]}

Milaneschi, Yuri ^{[39
]}

Palviainen, Teemu ^{[31
]}

Pearson, John F. ^{[40
]}

Peterson, Roseann E. ^{[21
]}

Ripatti, Samuli ^{[1
,2
,3
,31
,41
]}

机构：

[1] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[2] Harvard Med Sch, Boston, MA 02114 USA

[3] Broad Inst & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA

[4] Yale Sch Med, Dept Psychiat, West Haven, CT USA

[5] Vet Affairs Connecticut Healthcare Ctr, West Haven, CT USA

[6] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO USA

[7] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA

[8] Univ Edinburgh, Div Psychiat, Edinburgh, Midlothian, Scotland

[9] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA USA

[10] Virginia Commonwealth Univ, Coll Behav & Emot Hlth Inst, Richmond, VA USA

[11] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA USA

[12] Virginia Commonwealth Univ, Alcohol Res Ctr, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA USA

[13] Mayo Clin, Psychiat Genom & Pharmacogen Program, Rochester, MN USA

[14] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY USA

[15] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[16] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA

[17] State Univ New York, Dept Psychiat & Behav Sci, Downstate Med Ctr, Brooklyn, NY USA

[18] Univ Bonn, Inst Human Genet, Bonn, Germany

[19] Univ Bonn, Dept Gen, Life & Brain Ctr, Bonn, Germany

[20] Univ Utah, Dept Psychiat, Salt Lake City, UT USA

[21] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA USA

[22] 23andMe Inc, Mountain View, CA USA

[23] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany

[24] Martin Luther Univ Halle Wittenberg, Dept Psychiat Psychotherapy & Psychosomat, Halle, Germany

[25] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[26] Emory Univ, Dept Psychiat & Behav Sci, Sch Med, Atlanta, GA 30322 USA

[27] Univ Basel Hosp, Inst Med Genet & Pathol, Univ Basel, Human Genom Res Grp,Dept Biomed, Basel, Switzerland

[28] NIH NIAAA, Neurogenet Lab, Bethesda, MD USA

[29] Vrije Univ Amsterdam, Amsterdam Publ Hlth Res Inst, Dept Biol Psychol, Amsterdam, Netherlands

[30] Univ Otago, Christchurch, New Zealand

[31] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

[32] Univ Helsinki, Helsinki Collegium Adv Studies, Helsinki, Finland

[33] Univ Helsinki, Dept Psychol & Logoped, Helsinki, Finland

[34] Indiana Univ, Dept Med & Mol Genet, Sch Med, Indianapolis, IN 46204 USA

[35] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA

[36] Univ Edinburgh, Div Psychiat, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[37] Univ Colorado, Dept Integrat Physiol, Boulder, CO USA

[38] Suny Downstate Med Ctr, Dept Psychiat & Behav Sci, Henri Begleiter Neurodynam Lab, Brooklyn, NY 11203 USA

[39] Vrije Univ Amsterdam, Med Ctr GGz inGeest, Amsterdam Publ Hlth Res Inst, Dept Psychiat, Amsterdam, Netherlands

[40] Univ Otago, Biostat & Computat Biol Unit, Christchurch, New Zealand

[41] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland

[42] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[43] Washington Univ, Sch Med, Dept Genet, St Louis, MO USA

[44] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA

[45] NIAAA, Off Clin Director, NIH, Bethesda, MD USA

[46] Boston Univ, Dept Med Biomed Genet, Sch Med, Boston, MA USA

[47] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[48] Harvard Univ, Dept Sociol, Cambridge, MA USA

[49] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA

[50] Univ Colorado, Inst Behav Sci, Boulder, CO USA

来源：

NATURE NEUROSCIENCE | 2018年 / 21卷 / 12期

基金：

芬兰科学院; 英国惠康基金; 澳大利亚国家健康与医学研究理事会; 美国国家卫生研究院; 英国医学研究理事会; 澳大利亚研究理事会; 瑞典研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; NATIONAL EPIDEMIOLOGIC SURVEY; LD SCORE REGRESSION; RISK; METAANALYSIS; HERITABILITY; CONSUMPTION; ADH1B; PARTICIPANTS; COMORBIDITY;

D O I：

10.1038/s41593-018-0275-1

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1656 / +

页数：16

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