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Analysis of shared heritability in common disorders of the brain
ILAE Consortium on Complex Epilepsies,
METASTROKE and Intracerebral Hemorrhage Studies of the International Stroke Genetics Consortium,
Attention-Deficit Hyperactivity Disorder Working Group of the Psychiatric Genomics Consortium,
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium,
Bipolar Disorders Working Group of the Psychiatric Genomics Consortium,
Eating Disorders Working Group of the Psychiatric Genomics Consortium,
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium,
Tourette Syndrome and Obsessive Compulsive Disorder Working Group of the Psychiatric Genomics Consortium,
Schizophrenia Working Group of the Psychiatric Genomics Consortium,
on behalf of the Brainstorm consortium
Posted 16 Apr 2016
bioRxiv DOI: 10.1101/048991 (published DOI: 10.1126/science.aap8757)
Posted 16 Apr 2016
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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