Common variants on Xq28 conferring risk of schizophrenia in Han Chinese.

Abstract

Schizophrenia is a highly heritable, severe psychiatric disorder affecting approximately 1% of the world population. A substantial portion of heritability is still unexplained and the pathophysiology of schizophrenia remains to be elucidated. To identify more schizophrenia susceptibility loci, we performed a genome-wide association study (GWAS) on 498 patients with schizophrenia and 2025 controls from the Han Chinese population, and a follow-up study on 1027 cases and 1005 controls. In the follow-up study, we included 384 single nucleotide polymorphisms (SNPs) which were selected from the top hits in our GWAS (130 SNPs) and from previously implicated loci for schizophrenia based on the SZGene database, NHGRI GWAS Catalog, copy number variation studies, GWAS meta-analysis results from the international Psychiatric Genomics Consortium (PGC) and candidate genes from plausible biological pathways (254 SNPs). Within the chromosomal region Xq28, SNP rs2269372 in RENBP achieved genome-wide significance with a combined P value of 3.98 × 10(-8) (OR of allele A = 1.31). SNPs with suggestive P values were identified within 2 genes that have been previously implicated in schizophrenia, MECP2 (rs2734647, P combined = 8.78 × 10(-7), OR = 1.28; rs2239464, P combined = 6.71 × 10(-6), OR = 1.26) and ARHGAP4 (rs2269368, P combined = 4.74 × 10(-7), OR = 1.25). In addition, the patient sample in our follow-up study showed a significantly greater burden for pre-defined risk alleles based on the SNPs selected than the controls. This indicates the existence of schizophrenia susceptibility loci among the SNPs we selected. This also further supports multigenic inheritance in schizophrenia. Our findings identified a new schizophrenia susceptibility locus on Xq28, which harbor the genes RENBP, MECP2, and ARHGAP4.

DOI: 10.1093/schbul/sbt104
02004002014201520162017
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@article{Wong2014CommonVO, title={Common variants on Xq28 conferring risk of schizophrenia in Han Chinese.}, author={Emily Hoi-Man Wong and Hon-Cheong So and Miaoxin Li and Quang Wang and Amy W. Butler and Basil Paul and Hei-Man Wu and Tomy C. K. Hui and Siu-Chung Choi and Man-ting So and Maria-Merc{\`e} Garcia-Barcelo and Grainne M. McAlonan and Eric Chen and Eric F. C. Cheung and Raymond C. K. Chan and Shaun M Purcell and Stacey Shawn Cherny and Ronald R L Chen and Tao Li and Pak C. Sham}, journal={Schizophrenia bulletin}, year={2014}, volume={40 4}, pages={777-86} }