Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

被引：1644

作者：

Lee, S. Hong ^{[1
]}

Ripke, Stephan ^{[2
,3
,4
]}

Neale, Benjamin M. ^{[2
,3
,4
]}

Faraone, Stephen V. ^{[5
,6
]}

Purcell, Shaun M. ^{[2
,3
,4
,7
]}

Perlis, Roy H. ^{[4
,8
]}

Mowry, Bryan J. ^{[1
,9
]}

Thapar, Anita ^{[10
,11
]}

Goddard, Michael E. ^{[12
,13
]}

Witte, John S. ^{[14
]}

Absher, Devin ^{[15
]}

Agartz, Ingrid ^{[16
,17
]}

Akil, Huda ^{[18
]}

Amin, Farooq ^{[19
]}

Andreassen, Ole A. ^{[16
,20
]}

Anjorin, Adebayo ^{[21
]}

Anney, Richard ^{[22
]}

Anttila, Verneri ^{[2
,3
]}

Arking, Dan E. ^{[23
]}

Asherson, Philip ^{[24
]}

Azevedo, Maria H. ^{[25
]}

Backlund, Lena ^{[26
]}

Badner, Judith A. ^{[27
]}

Bailey, Anthony J. ^{[28
]}

Banaschewski, Tobias ^{[29
]}

Barchas, Jack D. ^{[30
]}

Barnes, Michael R. ^{[31
]}

Barrett, Thomas B. ^{[32
]}

Bass, Nicholas ^{[21
]}

Battaglia, Agatino ^{[33
]}

Bauer, Michael ^{[34
]}

Bayes, Monica ^{[35
]}

Bellivier, Frank ^{[36
,37
,38
,39
]}

Bergen, Sarah E. ^{[4
,8
,40
]}

Berrettini, Wade ^{[41
]}

Betancur, Catalina ^{[42
,43
,44
]}

Bettecken, Thomas ^{[45
]}

Biederman, Joseph ^{[46
]}

Binder, Elisabeth B. ^{[45
]}

Black, Donald W. ^{[47
]}

Blackwood, Douglas H. R. ^{[48
]}

Bloss, Cinnamon S. ^{[49
,50
]}

Boehnke, Michael ^{[51
,52
]}

Boomsma, Dorret I. ^{[53
,54
,55
]}

Breen, Gerome ^{[24
,56
,57
,58
]}

Breuer, Rene ^{[59
]}

Bruggeman, Richard ^{[60
]}

Cormican, Paul ^{[22
]}

Buccola, Nancy G. ^{[61
]}

Buitelaar, Jan K. ^{[62
]}

机构：

[1] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[2] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[3] Harvard Univ, Sch Med, Boston, MA USA

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

[5] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA

[6] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA

[7] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY USA

[8] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA

[9] Queensland Ctr Mental Hlth Res, Wacol, Qld, Australia

[10] Cardiff Univ, Sch Med, MRC, Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales

[11] Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales

[12] Dept Environm & Primary Ind Victoria, Biosci Res Div, Melbourne, Vic, Australia

[13] Univ Melbourne, Fac Land & Environm, Melbourne, Vic, Australia

[14] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[15] HudsonAlpha Inst Biotechnol, Huntsville, AL USA

[16] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, Oslo, Norway

[17] Diakonhjemmet Hosp, Dept Res, Oslo, Norway

[18] Univ Michigan, Mol & Behav Neurosci Inst, Mol Psychiat Lab, Ann Arbor, MI 48109 USA

[19] Emory Univ, Atlanta Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA

[20] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway

[21] UCL, Mental Hlth Sci Unit, London, England

[22] Univ Dublin Trinity Coll, Dept Psychiat, Dublin 2, Ireland

[23] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA

[24] Kings Coll London, Inst Psychiat, MRC, Social Genet & Dev Psychiat SGDP Ctr, London, England

[25] Univ Coimbra, Fac Med, Coimbra, Portugal

[26] Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden

[27] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA

[28] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada

[29] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, Mannheim, Germany

[30] Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY 10021 USA

[31] GlaxoSmithKline, London, England

[32] Portland VA Med Ctr, Portland, OR USA

[33] Stella Maris Inst Child & Adolescent Neuropsychia, Pisa, Italy

[34] Carl Gustav Carus Univ Hosp, Dept Psychiat & Psychotherapy, Dresden, Germany

[35] Parc Cient Barcelona, Ctr Nacl Anal Genom, Barcelona, Spain

[36] Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France

[37] Univ Paris 07, Paris, France

[38] Grp Hosp St Louis, AP HP, Dept Psychiat, Paris, France

[39] Fdn FondaMental, ENBREC European Network Bipolar Res Expert Ctr Gr, Creteil, France

[40] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[41] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA

[42] INSERM, U952, Paris, France

[43] CNRS, Unite Mixte Rech UMR 7224, Paris, France

[44] Univ Paris 06, Paris, France

[45] Max Planck Inst Psychiat, D-80804 Munich, Germany

[46] Massachusetts Gen Hosp, Clin & Res Programs Pediat Psychopharmacol & Adul, Boston, MA 02114 USA

[47] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA

[48] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland

[49] Scripps Translat Sci Inst, La Jolla, CA USA

[50] Scripps Hlth, La Jolla, CA USA

来源：

NATURE GENETICS | 2013年 / 45卷 / 09期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; BIPOLAR DISORDER; COMMON SNPS; SCHIZOPHRENIA; RISK; HERITABILITY; ASSOCIATION; VARIANTS;

D O I：

10.1038/ng.2711

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 +/- 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 +/- 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 +/- 0.06 s.e.), and ADHD and major depressive disorder (0.32 +/- 0.07 s.e.), low between schizophrenia and ASD (0.16 +/- 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

引用

页码：984 / +

页数：12

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