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

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.

doi:10.1038/s41588-018-0059-2

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

Date

2018

Authors

Pardiñas, A.

Holmans, P.

Pocklington, A.

Escott-Price, V.

Ripke, S.

Carrera, N.

Legge, S.

Bishop, S.

Cameron, D.

Hamshere, M.

Type:

Journal article

Citation

Nature Genetics, 2018; 50(3):381-389

Statement of Responsibility

Antonio F. Pardiñas, Peter Holmans, Andrew J. Pocklington, Valentina Escott-Price, Stephan Ripke … Bernhard T Baune … et al.

DOI

10.1038/s41588-018-0059-2

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.

Rights

Grant ID

Published Version

https://doi.org/10.1038/s41588-018-0059-2

Persistent link to this record

http://hdl.handle.net/2440/111860

Full item page

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

Date

Authors

Editors

Advisors

Journal Title

Journal ISSN

Volume Title

Type:

Citation

Statement of Responsibility

Conference Name

DOI

Abstract

School/Discipline

Dissertation Note

Provenance

Description

Access Status

Rights

License

Grant ID

Published Version

Call number

Persistent link to this record