Analysis of shared heritability in common disorders of the brain

Brainstorm Consortium, Verneri Anttila, Brendan Bulik-Sullivan, Hilary K Finucane, Raymond K Walters, Jose Bras, Laramie Duncan, Valentina Escott-Price, Guido J Falcone, Padhraig Gormley, Rainer Malik, Nikolaos A Patsopoulos, Stephan Ripke, Zhi Wei, Dongmei Yu, Phil H Lee, Patrick Turley, Benjamin Grenier-Boley, Vincent Chouraki, Yoichiro KamataniClaudine Berr, Luc Letenneur, Didier Hannequin, Philippe Amouyel, Anne Boland, Jean-François Deleuze, Emmanuelle Duron, Badri N Vardarajan, Christiane Reitz, Alison M Goate, Matthew J Huentelman, M Ilyas Kamboh, Eric B Larson, Ekaterina Rogaeva, Peter St George-Hyslop, Hakon Hakonarson, Walter A Kukull, Lindsay A Farrer, Lisa L Barnes, Thomas G Beach, F Yesim Demirci, Elizabeth Head, Christine M Hulette, Gregory A Jicha, John S K Kauwe, Jeffrey A Kaye, Amanda G Smith, Keith Matthews, Andrew McIntosh, Mary M Robertson, David Cohen

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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 numbereaap8757
Pages (from-to)1-15
Number of pages15
Issue number6395
Publication statusPublished - 22 Jun 2018


  • Brain Diseases/classification
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Mental Disorders/classification
  • Phenotype
  • Quantitative Trait, Heritable
  • Risk Factors

ASJC Scopus subject areas

  • General


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