- Title
- Combined analysis of exon splicing and genome wide polymorphism data predict schizophrenia risk loci.
- Creator
- Oldmeadow, Christopher; Mossman, David; Evans, Tiffany-Jane; Holliday, Elizabeth G.; Tooney, Paul A.; Cairns, Murray J.; Wu, Jingqin; Carr, Vaughan; Attia, John R.; Scott, Rodney J.
- Relation
- Journal of Psychiatric Research Vol. 52, p. 44-49
- Publisher Link
- http://dx.doi.org/10.1016/j.jpsychires.2014.01.011
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2014
- Description
- Schizophrenia has a strong genetic basis, and genome-wide association studies (GWAS) have shown that effect sizes for individual genetic variants which increase disease risk are small, making detection and validation of true disease-associated risk variants extremely challenging. Specifically, we first identify genes with exons showing differential expression between cases and controls, indicating a splicing mechanism that may contribute to variation in disease risk and focus on those showing consistent differential expression between blood and brain tissue. We then perform a genome-wide screen for SNPs associated with both normalised exon intensity of these genes (so called splicing QTLs) as well as association with schizophrenia. We identified a number of significantly associated loci with a biologically plausible role in schizophrenia, including MCPH1, DLG3, ZC3H13, and BICD2, and additional loci that influence splicing of these genes, including YWHAH. Our approach of integrating genome-wide exon intensity with genome-wide polymorphism data has identified a number of plausible SZ associated loci.
- Subject
- Schizophrenia; genetics; GWAS; alternative splicing; exons; phosphorylation
- Identifier
- http://hdl.handle.net/1959.13/1063744
- Identifier
- uon:17373
- Identifier
- ISSN:1879-1379
- Language
- eng
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