TY - JOUR
T1 - Analysis of shared heritability in common disorders of the brain
AU - 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 - Kamboh, M Ilyas
AU - Larson, Eric B
AU - Rogaeva, Ekaterina
AU - St George-Hyslop, Peter
AU - Hakonarson, Hakon
AU - Kukull, Walter A
AU - Farrer, Lindsay A
AU - Barnes, Lisa L
AU - Beach, Thomas G
AU - Demirci, F Yesim
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 - Pankratz, Vernon S
AU - Thomas, G Neil
N1 - Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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.
U2 - 10.1126/science.aap8757
DO - 10.1126/science.aap8757
M3 - Article
C2 - 29930110
SN - 0036-8075
VL - 360
JO - Science
JF - Science
IS - 6395
M1 - eaap8757
ER -