TY - JOUR
T1 - Analysis of shared heritability in common disorders of the brain
AU - The Brainstorm Consortium
AU - Anttila, Verneri
AU - Bulik-Sullivan, Brendan
AU - Finucane, Hilary K.
AU - Walters, Raymond K.
AU - Bras, Jose
AU - Duncan, Laramie
AU - Escott-Price, Valentina
AU - Falcone, Guido J.
AU - Gormley, Padhraig
AU - Malik, Rainer
AU - Patsopoulos, Nikolaos A.
AU - Ripke, Stephan
AU - Wei, Zhi
AU - Yu, Dongmei
AU - Lee, Phil H.
AU - Turley, Patrick
AU - Grenier-Boley, Benjamin
AU - Chouraki, Vincent
AU - Kamatani, Yoichiro
AU - Berr, Claudine
AU - Letenneur, Luc
AU - Hannequin, Didier
AU - Amouyel, Philippe
AU - Boland, Anne
AU - Deleuze, Jean François
AU - Duron, Emmanuelle
AU - Vardarajan, Badri N.
AU - Reitz, Christiane
AU - Goate, Alison M.
AU - Huentelman, Matthew J.
AU - Ilyas Kamboh, M.
AU - Larson, Eric B.
AU - Rogaeva, Ekaterina
AU - George-Hyslop, Peter St
AU - Hakonarson, Hakon
AU - Kukull, Walter A.
AU - Farrer, Lindsay A.
AU - Barnes, Lisa L.
AU - Beach, Thomas G.
AU - Yesim Demirci, F.
AU - Head, Elizabeth
AU - Hulette, Christine M.
AU - Jicha, Gregory A.
AU - Kauwe, John S.K.
AU - Kaye, Jeffrey A.
AU - Leverenz, James B.
AU - Levey, Allan I.
AU - Lieberman, Andrew P.
AU - Ruiz, Agustin
AU - Seshadri, Sudha
N1 - Publisher Copyright:
© 2018 American Association for the Advancement of Science. All rights reserved.
PY - 2018/6/22
Y1 - 2018/6/22
N2 - 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.
AB - 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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U2 - 10.1126/science.aap8757
DO - 10.1126/science.aap8757
M3 - Article
C2 - 29930110
AN - SCOPUS:85049284114
SN - 0036-8075
VL - 360
JO - Science
JF - Science
IS - 6395
M1 - 8757
ER -