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Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection

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Authors
Pardiñas, Antonio F.
Holmans, Peter
Pocklington, Andrew J.
Escott-Price, Valentina
Ripke, Stephan
Carrera, Noa
Legge, Sophie E.
Bishop, Sophie
Cameron, Darren
Hamshere, Marian L.
Han, Jun
Hubbard, Leon
Lynham, Amy
Mantripragada, Kiran
Rees, Elliott
MacCabe, James H.
McCarroll, Steven A.
Baune, Bernhard T.
Breen, Gerome
Byrne, Enda M.
Dannlowski, Udo
Eley, Thalia C.
Hayward, Caroline
Martin, Nicholas G.
McIntosh, Andrew M.
Plomin, Robert
Porteous, David J.
Wray, Naomi R.
Caballero, Armando
Geschwind, Daniel H.
Huckins, Laura M.
Ruderfer, Douglas M.
Santiago, Enrique
Sklar, Pamela
Stahl, Eli A.
Won, Hyejung
Agerbo, Esben
Als, Thomas D.
Andreassen, Ole A.
Bækvad-Hansen, Marie
Mortensen, Preben Bo
Pedersen, Carsten Bøcker
Børglum, Anders D.
Bybjerg-Grauholm, Jonas
Djurovic, Srdjan
Durmishi, Naser
Pedersen, Marianne Giørtz
Golimbet, Vera
Grove, Jakob
Hougaard, David M.
Mattheisen, Manuel
Molden, Espen
Mors, Ole
Nordentoft, Merete
Pejovic-Milovancevic, Milica
Sigurdsson, Engilbert
Silagadze, Teimuraz
Hansen, Christine Søholm
Stefansson, Kari
Stefansson, Hreinn
Steinberg, Stacy
Tosato, Sarah
Werge, Thomas
Collier, David A.
Rujescu, Dan
Kirov, George
Owen, Michael J.
O’Donovan, Michael C.
Walters, James T. R.
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Issue Date
2018-02-26

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Citation
Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection 2018, 50 (3):381 Nature Genetics
Abstract
Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population.
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To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files
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http://www.nature.com/articles/s41588-018-0059-2
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Archived with thanks to Nature Genetics
ae974a485f413a2113503eed53cd6c53
10.1038/s41588-018-0059-2
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English Journal Articles (Peer Reviewed)

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