Analysis of shared heritability in common disorders of the brain

被引：1188

作者：

Anttila, Verneri ^{[2
,3
,4
]}

Bulik-Sullivan, Brendan ^{[1
,2
,4
]}

Finucane, Hilary K. ^{[3
,4
,5
,6
]}

Walters, Raymond K. ^{[1
,2
,3
,4
]}

Bras, Jose ^{[7
,8
]}

Duncan, Laramie ^{[1
,2
,3
,4
,9
]}

Escott-Price, Valentina ^{[10
,11
]}

Falcone, Guido J. ^{[12
,13
,14
]}

Gormley, Padhraig ^{[1
,2
,3
,4
,12
]}

Malik, Rainer ^{[15
]}

Patsopoulos, Nikolaos A. ^{[4
,16
]}

Ripke, Stephan ^{[2
,3
,4
,17
]}

Wei, Zhi ^{[18
]}

Yu, Dongmei ^{[3
,12
]}

Lee, Phil H. ^{[3
,12
]}

Turley, Patrick ^{[14
]}

Grenier-Boley, Benjamin ^{[19
,20
,21
]}

Chouraki, Vincent ^{[19
,20
,21
,22
]}

Kamatani, Yoichiro ^{[23
,24
]}

Berr, Claudine ^{[25
,26
,27
]}

Letenneur, Luc ^{[28
,29
]}

Hannequin, Didier ^{[30
,31
]}

Amouyel, Philippe ^{[19
,20
,21
,22
]}

Boland, Anne ^{[32
]}

Deleuze, Jean-Francois ^{[32
]}

Duron, Emmanuelle ^{[33
,34
]}

Vardarajan, Badri N. ^{[35
,36
]}

Reitz, Christiane ^{[37
]}

Goate, Alison M. ^{[38
]}

Huentelman, Matthew J. ^{[39
]}

Kamboh, M. Ilyas ^{[40
]}

Larson, Eric B. ^{[41
,42
]}

Rogaeva, Ekaterina ^{[43
]}

St George-Hyslop, Peter ^{[43
,44
]}

Hakonarson, Hakon ^{[45
,46
,47
]}

Kukull, Walter A. ^{[48
]}

Farrer, Lindsay A. ^{[49
]}

Barnes, Lisa L. ^{[50
,51
,52
]}

Beach, Thomas G. ^{[53
]}

Demirci, F. Yesim ^{[40
]}

Head, Elizabeth ^{[54
]}

Hulette, Christine M. ^{[55
]}

Jicha, Gregory A. ^{[56
]}

Kauwe, John S. K. ^{[57
]}

Kaye, Jeffrey A. ^{[58
]}

Leverenz, James B. ^{[59
]}

Levey, Allan I. ^{[60
]}

Lieberman, Andrew P. ^{[61
]}

Pankratz, Vernon S. ^{[62
]}

Poon, Wayne W. ^{[63
]}

机构：

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

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA

[4] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA

[5] MIT, Dept Math, Cambridge, MA 02139 USA

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

[7] UCL, UK Dementia Res Inst, London, England

[8] UCL, Dept Mol Neurosci, Inst Neurol, London, England

[9] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[10] Cardiff Univ, Med Res Council Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales

[11] Cardiff Univ, Dementia Res Inst, Cardiff, S Glam, Wales

[12] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA

[13] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[14] Harvard Med Sch, Boston, MA USA

[15] Ludwig Maximilians Univ Munchen, Univ Hosp, Inst Stroke & Dementia Res ISD, Munich, Germany

[16] Harvard Med Sch, Dept Neurol, Brigham & Womens Hosp, Boston, MA USA

[17] Charite Univ Med Berlin, Berlin, Germany

[18] New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA

[19] INSERM, U1167, LabEx, DISTALZ, Lille, France

[20] Inst Pasteur, U1167, Lille, France

[21] Univ Lille, Risk Factors & Mol Determinants Aging Related Dis, U1167, RID,AGE, Lille, France

[22] Ctr Hosp Univ, Lille, France

[23] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan

[24] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan

[25] INSERM, U1061, Neuropsychiat Epidemiol & Clin Res, Montpellier, France

[26] Univ Montpellier, Montpellier, France

[27] Montpellier Univ, Hosp Gui Chauliac, Memory Res & Resources Ctr, Dept Neurol, Montpellier, France

[28] INSERM, UMR 1219, Bordeaux, France

[29] Univ Bordeaux, Bordeaux, France

[30] Rouen Univ Hosp, Rouen, France

[31] INSERM, U1245, Rouen, France

[32] CEA, Inst Biol Francois Jacob, CNRGH, Evry, France

[33] Hop Broca, AP HP, Dept Gerontol, Paris, France

[34] Univ Paris Sud XI, Hop Paul Brousse, Le Kremlin Bicetre, Paris, France

[35] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY USA

[36] Columbia Univ, Dept Neurol, New York, NY USA

[37] Columbia Univ, New York, NY USA

[38] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA

[39] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA

[40] Univ Pittsburgh, Pittsburgh, PA USA

[41] Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA

[42] Univ Washington, Dept Med, Seattle, WA 98195 USA

[43] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada

[44] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England

[45] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA

[46] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA

[47] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA

[48] Univ Washington, Dept Epidemiol, NACC, Seattle, WA 98195 USA

[49] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA

[50] Rush Alzheimers Dis Ctr, Chicago, IL USA

来源：

SCIENCE | 2018年 / 360卷 / 6395期

关键词：

GENOME-WIDE ASSOCIATION; DEFICIT HYPERACTIVITY DISORDER; LONG-TERM SURVIVAL; BODY-MASS INDEX; BIPOLAR DISORDER; GENETIC CORRELATIONS; SUSCEPTIBILITY LOCI; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; ANOREXIA-NERVOSA;

D O I：

10.1126/science.aap8757

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

引用

页码：1313 / +

页数：13

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