Science.: co-auth.: group Reymond

 2018 Jun 22;360(6395). pii: eaap8757. doi: 10.1126/science.aap8757.

Analysis of shared heritability in common disorders of the brain.

Brainstorm ConsortiumAnttila VBulik-Sullivan BFinucane HKWalters RKBras JDuncan LEscott-Price VFalcone GJGormley PMalik RPatsopoulos NARipke SWei ZYu DLee PHTurley PGrenier-Boley BChouraki VKamatani YBerr CLetenneur LHannequin DAmouyel PBoland ADeleuze JFDuron EVardarajan BNReitz CGoate AMHuentelman MJKamboh MILarson EBRogaeva ESt George-Hyslop PHakonarson HKukull WAFarrer LABarnes LLBeach TGDemirci FYHead EHulette CMJicha GAKauwe JSKKaye JALeverenz JBLevey AILieberman APPankratz VSPoon WWQuinn JFSaykin AJSchneider LSSmith AGSonnen JAStern RAVan Deerlin VMVan Eldik LJHarold DRusso GRubinsztein DCBayer ATsolaki MProitsi PFox NCHampel HOwen MJMead SPassmore PMorgan KNöthen MMRossor MLupton MKHoffmann PKornhuber JLawlor BMcQuillin AAl-Chalabi ABis JCRuiz ABoada MSeshadri SBeiser ARice Kvan der Lee SJDe Jager PLGeschwind DHRiemenschneider MRiedel-Heller SRotter JIRansmayr GHyman BTCruchaga CAlegret MWinsvold BPalta PFarh KHCuenca-Leon EFurlotte NKurth TLigthart LTerwindt GMFreilinger TRan 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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.

PMID: 29930110