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https://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. |
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 |
Published version: | http://dx.doi.org/10.1038/s41588-018-0059-2 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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