Analysis of shared heritability in common disorders of the brain

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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
Issue number6395
StatePublished - Jun 22 2018

Bibliographical note

Funding Information:
We thank the members of the Neale and Daly laboratories for helpful discussions; R. Hoskins, J. Wessman, and J. Martin for comments on the manuscript; M. Whittall for inspiration; S. Knemeye for help with the summary figure; C. Hammond for organizational assistance; and the patients and participants of the respective consortia for their participation. Data on coronary artery disease have been contributed by CARDIoGRAMplusC4D investigators and have been downloaded from matSpD (Matrix Spectral Decomposition method) is available at This research was conducted using the UK Biobank resource (application 18597). This work was supported by grants 1R01MH10764901 and 5U01MH09443203 from the National Institute of Mental Health, as well as the Orion Farmos Research Foundation (V.A.) and the Fannie and John Hertz Foundation (H.K.F.). Consortium specific funding is detailed in the supplementary materials (“Study-specific acknowledgments”).

Publisher Copyright:
© 2018 American Association for the Advancement of Science. All rights reserved.

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