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New paper in Mol Psychiatry - Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population.

Mol Psychiatry. 2016 Dec 6. doi: 10.1038/mp.2016.212. [Epub ahead of print]
Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population.
Yu H, Yan H, Li J, Li Z, Zhang X, Ma Y, Mei L, Liu C, Cai L, Wang Q, Zhang F, Iwata N, Ikeda M, Wang L, Lu T; Chinese Schizophrenia Collaboration Group, Li M, Xu H, Wu X, Liu B, Yang J, Li K, Lv L, Ma X, Wang C, Li L, Yang F, Jiang T, Shi Y, Li T, Zhang D, Yue W.


Abstract
Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10-12, odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10-10, OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10-10, OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10-9, OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case-control status in the Chinese population (Nagelkerke R2: 1.7% ~5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.

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