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 - Pankratz, Vernon S.
AU - Seshadri, Sudha
N1 - Funding Information:
We thank the members of the Neale and Daly laboratories for helpful discussions; R. Hoskins, J. Wessman, and J. Martin for comments on the manuscript; M. Whittall for inspiration; S. Knemeye for help with the summary figure; C. Hammond for organizational assistance; and the patients and participants of the respective consortia for their participation. Data on coronary artery disease have been contributed by CARDIoGRAMplusC4D investigators and have been downloaded from www.cardiogramplusc4d.org. matSpD (Matrix Spectral Decomposition method) is available at neurogenetics.qimrberghofer.edu.au/matSpD/. This research was conducted using the UK Biobank resource (application 18597). This work was supported by grants 1R01MH10764901 and 5U01MH09443203 from the National Institute of Mental Health, as well as the Orion Farmos Research Foundation (V.A.) and the Fannie and John Hertz Foundation (H.K.F.). Consortium specific funding is detailed in the supplementary materials (“Study-specific acknowledgments”).
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.
UR - http://www.scopus.com/inward/record.url?scp=85049284114&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049284114&partnerID=8YFLogxK
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 -