title: Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population.
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.
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.|Department of Biochemistry, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health &National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: H
authors.identifier: 0000-0001-6549-3713
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Biochemistry, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health &National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: H
authors.identifier: 0000-0003-0376-9037
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Biochemistry, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health &National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: 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.|Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, China.|Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Shanghai, China.|The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.|National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: X
authors.identifier: 0000-0003-0262-7854
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health &National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Biochemistry, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health &National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Psychiatry, the University of Melbourne, Parkville, VIC, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: L
authors.initials: L
authors.lastname: Cai
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|State Key Laboratory of Biotherapy, Psychiatric laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Iwata
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Biochemistry, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health &National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health &National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: T
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, China.
authors.forename: M
authors.identifier: 0000-0002-8197-6552
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.|National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.affiliation: Tianjin Anding Hospital, Tianjin, China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Hebei Mental Health Center, Baoding, Hebei, China.
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.affiliation: The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: L
authors.initials: L
authors.lastname: Lv
authors.affiliation: Beijing Anding Hospital, Capital Medical University, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.affiliation: Beijing Anding Hospital, Capital Medical University, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: The Second Xiangya Hospital of Central South University, Changsha, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Beijing HuiLongGuan Hospital, Peking University, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.|National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: T
authors.identifier: 0000-0002-0607-3775
authors.initials: T
authors.lastname: Jiang
authors.affiliation: 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.|Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, China.|Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Shanghai, China.|The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|State Key Laboratory of Biotherapy, Psychiatric laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health &National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.|Peking-Tsinghua Joint Center for Life Sciences/PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health &National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Yue
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D005006:Ethnicity / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D018080:Receptors, GABA-B / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D018080:Receptors, GABA-B; D008780:Methyltransferases; C505756:AS3MT protein, human; D017346:Protein Serine-Threonine Kinases; C109891:VRK2 protein, human