期刊
JOURNAL OF PSYCHIATRIC RESEARCH
卷 52, 期 -, 页码 44-49出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jpsychires.2014.01.011
关键词
Schizophrenia; Genetics; GWAS; Alternative splicing; Exons; Phosphorylation
类别
资金
- Schizophrenia Research Institute
- Neurobehavioral Genetics Unit
- New South Wales Ministry of Health
- Schizophrenia Research Institute from the New South Wales Ministry of Health
- M.C. Ainsworth Research Fellowship in Epigenetics
- NHMRC
- Pratt Foundation
- Ramsay Health Care
- University of Sydney
- National Health and Medical Research Council of Australia
- National Institute of Alcohol Abuse and Alcoholism
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 axons 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 axon 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 axon intensity with genome-wide polymorphism data has identified a number of plausible SZ associated loci. (C) 2014 Elsevier Ltd. All rights reserved.
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