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Mol Psychiatry. 2017 Jul;22(7):954-960. doi: 10.1038/mp.2016.212. Epub 2016 Dec 6.

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

Yu H1,2,3, Yan H2,3, Li J2,3, Li Z4,5,6,7, Zhang X8,9, Ma Y2,3, Mei L2,3, Liu C10, Cai L4, Wang Q11,12, Zhang F13, Iwata N14, Ikeda M14, Wang L2,3, Lu T2,3; Chinese Schizophrenia Collaboration Group, Li M15, Xu H15, Wu X15, Liu B8,9, Yang J16, Li K17, Lv L18, Ma X19, Wang C19, Li L20, Yang F21, Jiang T8,9, Shi Y4,5,6,7, Li T11,12, Zhang D2,3,22, Yue W2,3.

Author information

1
Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
2
Department of Biochemistry, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.
3
Key Laboratory of Mental Health, Ministry of Health &National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
4
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education) and the Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai, China.
5
Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, China.
6
Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Shanghai, China.
7
The Affiliated Hospital of Qingdao University, Qingdao, China.
8
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
9
National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
10
Department of Psychiatry, the University of Melbourne, Parkville, VIC, Australia.
11
Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
12
State Key Laboratory of Biotherapy, Psychiatric laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
13
Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China.
14
Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan.
15
Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, China.
16
Tianjin Anding Hospital, Tianjin, China.
17
Hebei Mental Health Center, Baoding, Hebei, China.
18
The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China.
19
Beijing Anding Hospital, Capital Medical University, Beijing, China.
20
The Second Xiangya Hospital of Central South University, Changsha, China.
21
Beijing HuiLongGuan Hospital, Peking University, Beijing, China.
22
Peking-Tsinghua Joint Center for Life Sciences/PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.

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.

PMID:
27922604
DOI:
10.1038/mp.2016.212
[Indexed for MEDLINE]

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