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Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population
Yu, H. G1,2,3,4; Yan, H. K2,3,4; Li, J. M2,3,4; Li, Z. P5,6,7,8; Zhang, X. D10,11; Ma, Y. C2,3,4; Mei, L. R2,3,4; Liu, C. K12; Cai, L. T5,6; Wang, Q. V13,14; Zhang, F. S15; Iwata, N. D16; Ikeda, M. E16; Wang, L. P2,3,4; Lu, T. M2,3,4; Li, M. K18; Xu, H. R18; Wu, X. D18; Liu, B. C10,11; Yang, J. I19; Li, K. R20; Lv, L. N21; Ma, X. A22; Wang, C. T22; Li, L. P23; Yang, F. K24; Jiang, T. L10,11; Shi, Y. R5,6,7,8,9; Li, T. P13,14; Zhang, D. C2,3,4,25; Yue, W. T2,3,4; Chinese Schizophrenia Collaboratio
AbstractMany 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 x 10(-12), odds ratio (OR) = 1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P = 4.96 x 10(-10), OR = 0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P = 7.94 x 10(-10), OR = 0.87; rs10883765 at an intron of ARL3, P = 3.06 x 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 R-2: 1.7% similar to 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.
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Funding OrganizationNational Key Technology R&D Program of China(2015BAI13B01) ; National Natural Science Foundation of China(91232305 ; National High Technology Research and Development Program of China(2009AA022702) ; 81361120395 ; 91432304 ; 81571313)
WOS Research AreaBiochemistry & Molecular Biology ; Neurosciences & Neurology ; Psychiatry
WOS SubjectBiochemistry & Molecular Biology ; Neurosciences ; Psychiatry
WOS IDWOS:000403911900003
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Cited Times:10[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Affiliation1.Tsinghua Univ, Sch Life Sci, Tsinghua Peking Joint Ctr Life Sci, Beijing, Peoples R China
2.Peking Univ, Inst Mental Hlth, Hosp 6, Dept Biochem, 51 Hua Yuan Bei Rd, Beijing 100191, Peoples R China
3.Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing, Peoples R China
4.Peking Univ, Natl Clin Res Ctr Mental Disorders, Beijing, Peoples R China
5.Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Bio X Inst, Shanghai, Peoples R China
6.Shanghai Jiao Tong Univ, Collaborat Innovat Ctr Brain Sci, Shanghai, Peoples R China
7.Shanghai Jiao Tong Univ, Inst Social Cognit & Behav Sci, Shanghai, Peoples R China
8.Shanghai Jiao Tong Univ, Inst Neuropsychiat Sci & Syst Biol Med, Shanghai, Peoples R China
9.Qingdao Univ, Affiliated Hosp, Qingdao, Peoples R China
10.Chinese Acad Sci, Inst Automat, Brainnetome Ctr, Beijing, Peoples R China
11.Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing, Peoples R China
12.Univ Melbourne, Dept Psychiat, Parkville, Vic, Australia
13.Sichuan Univ, West China Hosp, Mental Hlth Ctr, Chengdu, Sichuan, Peoples R China
14.Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Psychiat Lab, Chengdu, Sichuan, Peoples R China
15.Nanjing Med Univ, Dept Clin Psychol, Wuxi Mental Hlth Ctr, Wuxi, Peoples R China
16.Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi, Japan
17.Chinese Acad Sci & Yunnan Prov, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Kunming, Yunnan, Peoples R China
18.Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Rheumatol & Immunol, Shanghai, Peoples R China
19.Tianjin Anding Hosp, Tianjin, Peoples R China
20.Hebei Mental Hlth Ctr, Baoding, Hebei, Peoples R China
21.Xinxiang Med Univ, Affiliated Hosp 2, Xinxiang, Henan, Peoples R China
22.Capital Med Univ, Beijing Anding Hosp, Beijing, Peoples R China
23.Cent S Univ, Xiangya Hosp 2, Changsha, Hunan, Peoples R China
24.Peking Univ, Beijing HuiLongGuan Hosp, Beijing, Peoples R China
25.Peking Univ, Peking Tsinghua Joint Ctr Life Sci, PKU IDG, McGovern Inst Brain Res, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Yu, H. G,Yan, H. K,Li, J. M,et al. Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population[J]. MOLECULAR PSYCHIATRY,2017,22(7):954-960.
APA Yu, H. G.,Yan, H. K.,Li, J. M.,Li, Z. P.,Zhang, X. D.,...&Chinese Schizophrenia Collaboratio.(2017).Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population.MOLECULAR PSYCHIATRY,22(7),954-960.
MLA Yu, H. G,et al."Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population".MOLECULAR PSYCHIATRY 22.7(2017):954-960.
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