Analysis of shared heritability in common disorders of the brain

The Brainstorm Consortium

Research output: Contribution to journalArticle

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 (US)
Article number8757
JournalScience
Volume360
Issue number6395
DOIs
StatePublished - Jun 22 2018

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

ASJC Scopus subject areas

  • General

Cite this

Analysis of shared heritability in common disorders of the brain. / The Brainstorm Consortium.

In: Science, Vol. 360, No. 6395, 8757, 22.06.2018.

Research output: Contribution to journalArticle

The Brainstorm Consortium. / Analysis of shared heritability in common disorders of the brain. In: Science. 2018 ; Vol. 360, No. 6395.
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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.",
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AU - Bras, Jose

AU - Duncan, Laramie

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AU - Falcone, Guido J.

AU - Gormley, Padhraig

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AU - Patsopoulos, Nikolaos A.

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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.

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AU - Beach, Thomas G.

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AU - Zandi, Peter P

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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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