Analysis of shared heritability in common disorders of the brain

Verneri Anttila; Brendan Bulik-Sullivan; Hilary Kiyo Finucane; Jose Bras; Laramie Duncan; Valentina Escott-Price; Guido Falcone; Padhraig Gormley; Rainer Malik; Nikolaos Patsopoulos; Stephan Ripke; Raymond Walters; Zhi Wei; Dongmei Yu; Phil Lee; IGAP consortium; IHGC consortium; ILAE Consortium on Complex Epilepsies; IMSGC consortium; IPDGC consortium; METASTROKE and ICH Studies of the ISGC; ADHD Working Group of the PGC; Anorexia Nervosa Working Group of the PGC; ASD Working Group of the PGC; Bipolar Disorders Working Group of the PGC; Major Depressive Disorder Working Group of the PGC; OCD and TS Working Group of the

doi:10.1101/048991

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bioRxiv · 10.1101/048991

Analysis of shared heritability in common disorders of the brain

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Abstract

Disorders of the brain exhibit considerable epidemiological comorbidity and frequently share symptoms, provoking debate about the extent of their etiologic overlap. We quantified the genetic sharing of 25 brain disorders based on summary statistics from genome-wide association studies of 215,683 patients and 657,164 controls, and their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders show substantial sharing of common variant risk, while neurological disorders appear more distinct from one another. We observe limited evidence of sharing between neurological and psychiatric disorders, but do identify robust sharing between disorders and several cognitive measures, as well as disorders and personality types. We also performed extensive simulations to explore how power, diagnostic misclassification and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a source of risk for brain disorders and the value of heritability-based methods in understanding their etiology.

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Verneri Anttila, Brendan Bulik-Sullivan, Hilary Kiyo Finucane, Jose Bras, Laramie Duncan, Valentina Escott-Price, Guido Falcone, Padhraig Gormley, Rainer Malik, Nikolaos Patsopoulos, Stephan Ripke, Raymond Walters, Zhi Wei, Dongmei Yu, Phil Lee, IGAP consortium, IHGC consortium, ILAE Consortium on Complex Epilepsies, IMSGC consortium, IPDGC consortium, METASTROKE and ICH Studies of the ISGC, ADHD Working Group of the PGC, Anorexia Nervosa Working Group of the PGC, ASD Working Group of the PGC, Bipolar Disorders Working Group of the PGC, Major Depressive Disorder Working Group of the PGC, OCD and TS Working Group of the. 2016-04-16. Analysis of shared heritability in common disorders of the brain. https://doi.org/10.1101/048991

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