Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/111860
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Type: Journal article
Title: Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection
Author: Pardiñas, A.
Holmans, P.
Pocklington, A.
Escott-Price, V.
Ripke, S.
Carrera, N.
Legge, S.
Bishop, S.
Cameron, D.
Hamshere, M.
Han, J.
Hubbard, L.
Lynham, A.
Mantripragada, K.
Rees, E.
MacCabe, J.
McCarroll, S.
Baune, B.
Breen, G.
Byrne, E.
et al.
Citation: Nature Genetics, 2018; 50(3):381-389
Publisher: Nature Publishing Group
Issue Date: 2018
ISSN: 1061-4036
1546-1718
Statement of
Responsibility: 
Antonio F. Pardiñas, Peter Holmans, Andrew J. Pocklington, Valentina Escott-Price, Stephan Ripke … Bernhard T Baune … et al.
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.
Keywords: GERAD1 Consortium; CRESTAR Consortium; Humans; Genetic Predisposition to Disease; Case-Control Studies; Schizophrenia; Gene Frequency; Inheritance Patterns; Polymorphism, Single Nucleotide; Alleles; Genes, Lethal; Genome-Wide Association Study; Selection, Genetic; Genetic Loci
Rights: © 2018 Nature America Inc., part of Springer Nature. All rights reserved.
RMID: 0030083897
DOI: 10.1038/s41588-018-0059-2
Grant ID: http://purl.org/au-research/grants/nhmrc/1078901
http://purl.org/au-research/grants/nhmrc/1053639
http://purl.org/au-research/grants/nhmrc/241944
http://purl.org/au-research/grants/nhmrc/339462
http://purl.org/au-research/grants/nhmrc/389875
http://purl.org/au-research/grants/nhmrc/389891
http://purl.org/au-research/grants/nhmrc/389892
http://purl.org/au-research/grants/nhmrc/389927
http://purl.org/au-research/grants/nhmrc/389938
http://purl.org/au-research/grants/nhmrc/442915
http://purl.org/au-research/grants/nhmrc/442981
http://purl.org/au-research/grants/nhmrc/496675
http://purl.org/au-research/grants/nhmrc/496739
http://purl.org/au-research/grants/nhmrc/552485
http://purl.org/au-research/grants/nhmrc/552498
http://purl.org/au-research/grants/nhmrc/613602
http://purl.org/au-research/grants/nhmrc/613608
http://purl.org/au-research/grants/nhmrc/613674
http://purl.org/au-research/grants/nhmrc/613667
http://purl.org/au-research/grants/arc/FT0991360
http://purl.org/au-research/grants/arc/FT0991022
Appears in Collections:Medicine publications

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