Analysis of shared heritability in common disorders of the brain

The Brainstorm Consortium

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number8757
Pages (from-to)1-15
Number of pages15
JournalScience
Volume360
Issue number6395
DOIs
Publication statusPublished - 22 Jun 2018

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Brain Diseases
Psychiatry
Phenotype
Genetic Heterogeneity
Genome-Wide Association Study
Nervous System Diseases
Comorbidity
Brain

Cite this

The Brainstorm Consortium. / Analysis of shared heritability in common disorders of the brain. In: Science. 2018 ; Vol. 360, No. 6395. pp. 1-15.
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title = "Analysis of shared heritability in common disorders of the brain",
abstract = "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.",
author = "Verneri Anttila and Brendan Bulik-Sullivan and Finucane, {Hilary K.} and Walters, {Raymond K.} and Jose Bras and Laramie Duncan and Valentina Escott-Price and Falcone, {Guido J.} and Padhraig Gormley and Rainer Malik and Patsopoulos, {Nikolaos A.} and Stephan Ripke and Zhi Wei and Dongmei Yu and Lee, {Phil H.} and Patrick Turley and Benjamin Grenier-Boley and Vincent Chouraki and Yoichiro Kamatani and Claudine Berr and Luc Letenneur and Didier Hannequin and Philippe Amouyel and Anne Boland and Deleuze, {Jean Fran{\cc}ois} and Emmanuelle Duron and Vardarajan, {Badri N.} and Christiane Reitz and Goate, {Alison M.} and Huentelman, {Matthew J.} and {Ilyas Kamboh}, M. and Larson, {Eric B.} and Ekaterina Rogaeva and George-Hyslop, {Peter St} and Hakon Hakonarson and Kukull, {Walter A.} and Farrer, {Lindsay A.} and Barnes, {Lisa L.} and Beach, {Thomas G.} and {Yesim Demirci}, F. and Elizabeth Head and Lannie Ligthart and Hottenga, {Jouke Jan} and Brenda Penninx and Dorret Boomsma and Middeldorp, {Christel M.} and Rick Jansen and {De Geus}, Eco and Beekman, {Aartjan T.F.} and Derks, {Eske M.} and {The Brainstorm Consortium}",
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Analysis of shared heritability in common disorders of the brain. / The Brainstorm Consortium.

In: Science, Vol. 360, No. 6395, 8757, 22.06.2018, p. 1-15.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Analysis of shared heritability in common disorders of the brain

AU - Anttila, Verneri

AU - Bulik-Sullivan, Brendan

AU - Finucane, Hilary K.

AU - Walters, Raymond K.

AU - Bras, Jose

AU - Duncan, Laramie

AU - Escott-Price, Valentina

AU - Falcone, Guido J.

AU - Gormley, Padhraig

AU - Malik, Rainer

AU - Patsopoulos, Nikolaos A.

AU - Ripke, Stephan

AU - Wei, Zhi

AU - Yu, Dongmei

AU - Lee, Phil H.

AU - Turley, Patrick

AU - Grenier-Boley, Benjamin

AU - Chouraki, Vincent

AU - Kamatani, Yoichiro

AU - Berr, Claudine

AU - Letenneur, Luc

AU - Hannequin, Didier

AU - Amouyel, Philippe

AU - Boland, Anne

AU - Deleuze, Jean François

AU - Duron, Emmanuelle

AU - Vardarajan, Badri N.

AU - Reitz, Christiane

AU - Goate, Alison M.

AU - Huentelman, Matthew J.

AU - Ilyas Kamboh, M.

AU - Larson, Eric B.

AU - Rogaeva, Ekaterina

AU - George-Hyslop, Peter St

AU - Hakonarson, Hakon

AU - Kukull, Walter A.

AU - Farrer, Lindsay A.

AU - Barnes, Lisa L.

AU - Beach, Thomas G.

AU - Yesim Demirci, F.

AU - Head, Elizabeth

AU - Ligthart, Lannie

AU - Hottenga, Jouke Jan

AU - Penninx, Brenda

AU - Boomsma, Dorret

AU - Middeldorp, Christel M.

AU - Jansen, Rick

AU - De Geus, Eco

AU - Beekman, Aartjan T.F.

AU - Derks, Eske M.

AU - The Brainstorm Consortium

N1 - Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2018/6/22

Y1 - 2018/6/22

N2 - 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.

AB - 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.

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U2 - 10.1126/science.aap8757

DO - 10.1126/science.aap8757

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