Analysis of shared heritability in common disorders of the brain
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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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The record
- Venue
- Science
- Topic
- Genetic Associations and Epidemiology
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Sunnybrook Health Science CentreUniversity of CalgaryBC Mental Health & Substance Use ServicesMontreal Neurological Institute and HospitalDalhousie UniversityUniversity of TorontoSickKids FoundationDouglas Mental Health University InstituteMcGill UniversityCentre Hospitalier de l’Université de MontréalUniversity of British ColumbiaHospital for Sick ChildrenUniversity Health NetworkOccupational Cancer Research Centre
- Funders
- National Institute of Mental HealthInstitute of Zoology, Chinese Academy of SciencesMenzies Centre for Australian Studies, King's College London, University of LondonNIHR Maudsley Biomedical Research CentreState University of New York Upstate Medical UniversityNational Institutes of HealthNovo Nordisk FondenUniversitätsklinikum JenaLee Kong Chian School of Medicine, Nanyang Technological UniversityState University of New YorkLundbeckfondenChinese University of Hong KongVirginia Commonwealth UniversityVetenskapsrådetAgence Nationale de la RechercheUniversiteit MaastrichtNational Center for Advancing Translational SciencesMedical Research CouncilUniversity of WollongongOxford Health NHS Foundation TrustNanyang Technological UniversityUniklinikum Giessen und MarburgKing's College LondonNational Institute of Neurological Disorders and StrokeSyracuse UniversityKunming Institute of Zoology, Chinese Academy of SciencesNSW Health PathologyNational University of SingaporeWellcome TrustUniversity College LondonUniversity of California, Santa BarbaraRoyal College of Surgeons in IrelandChinese Academy of SciencesUniversity of OxfordLawrence Berkeley National LaboratoryMotor Neurone Disease AssociationUniversity of North Carolina at Chapel HillParkinson's UKNorthShore University HealthSystemNational Institute on AgingNational Institute for Health and Care Research
- Keywords
- HeritabilityGenome-wide association studyMissing heritability problemEtiologyGenetic associationComorbidityTwin studyEpidemiologyPsychiatryPhenotypeMedicineClinical psychologyPsychologyBiologyGeneticsGenetic variantsSingle-nucleotide polymorphismInternal medicineGenotype
- Has abstract in OpenAlex
- yes