Analysis of shared heritability in common disorders of the brain

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 Kamatani, Claudine BerrLuc Letenneur, Didier Hannequin, Philippe Amouyel, Anne Boland, Jean-Francois 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, James B. Leverenz, Allan I. Levey, Andrew P. Lieberman, Vernon S. Pankratz, Wayne W. Poon, Klaus-Peter Lesch, Jim van Os, Brainstorm Consortium, Aiden Corvin*, Benjamin M. Neale*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

818 Citations (Web of Science)

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
Number of pages13
JournalScience
Volume360
Issue number6395
DOIs
Publication statusPublished - 22 Jun 2018

Keywords

  • GENOME-WIDE ASSOCIATION
  • DEFICIT HYPERACTIVITY DISORDER
  • MAJOR DEPRESSIVE DISORDER
  • POPULATION-BASED TWIN
  • LONG-TERM SURVIVAL
  • BODY-MASS INDEX
  • ALZHEIMERS-DISEASE
  • ANOREXIA-NERVOSA
  • BIPOLAR DISORDER
  • GENETIC CORRELATIONS
  • Genome-Wide Association Study
  • Quantitative Trait, Heritable
  • Humans
  • Risk Factors
  • Mental Disorders/classification
  • Genetic Variation
  • Phenotype
  • Brain Diseases/classification

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