| Title | Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals A Genome-Wide Association Study and Meta-analysis |
| Authors | Li, Hui-Juan Zhang, Chen Hui, Li Zhou, Dong-Sheng Li, Yi Zhang, Chu-Yi Wang, Chuang Wang, Lu Li, Wenqiang Yang, Yongfeng Qu, Na Tang, Jinsong He, Ying Zhou, Jun Yang, Zihao Li, Xingxing Cai, Jun Yang, Lu Chen, Jun Fan, Weixing Tang, Wei Tang, Wenxin Jia, Qiu-Fang Liu, Weiqing Zhuo, Chuanjun Song, Xueqin Liu, Fang Bai, Yan Zhong, Bao-Liang Zhang, Shu-Fang Chen, Jing Xia, Bin Lv, Luxian Liu, Zhongchun Hu, Shaohua Li, Xiao-Yan Liu, Jie-Wei Cai, Xin Yao, Yong-Gang Zhang, Yuyanan Yan, Hao Chang, Suhua Zhao, Jing-Ping Yue, Wei-Hua Luo, Xiong-Jian Chen, Xiaogang Xiao, Xiao Fang, Yiru Li, Ming |
| Affiliation | Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming Inst Zool, Chinese Acad Sci & Yunnan Prov, 32 Jiao Chang Donglu, Kunming 650223, Yunnan, Peoples R China Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming, Yunnan, Peoples R China Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Clin Res Ctr, Sch Med, 600 S Wanping Rd, Shanghai 200030, Peoples R China Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Div Mood Disorders, Sch Med, 600 S Wanping Rd, Shanghai 200030, Peoples R China Shanghai Key Lab Psychot Disorders, Shanghai, Peoples R China Soochow Univ, Suzhou Guangji Hosp, Affiliated Guangji Hosp, Suzhou, Jiangsu, Peoples R China Ningbo Kangning Hosp, Dept Psychiat, Ningbo, Zhejiang, Peoples R China Huazhong Univ Sci & Technol, Tongji Med Coll, Affiliated Wuhan Mental Hlth Ctr, Wuhan, Hubei, Peoples R China China Univ Geosci, Res Ctr Psychol & Hlth Sci, Wuhan, Hubei, Peoples R China Ningbo Univ, Sch Med, Dept Pharmacol, Ningbo, Zhejiang, Peoples R China Ningbo Univ, Prov Key Lab Pathophysiol, Dept Pharmacol, Ningbo, Zhejiang, Peoples R China Xinxiang Med Univ, Henan Mental Hosp, Affiliated Hosp 2, Xinxiang, Henan, Peoples R China Xinxiang Med Univ, Henan Key Lab Biol Psychiat, Int Joint Res Lab Psychiat & Neurosci Henan, Xinxiang, Henan, Peoples R China Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Psychiat, Hangzhou, Zhejiang, Peoples R China Key Lab Med Neurobiol Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China Cent South Univ, Xiangya Hosp 2, Dept Psychiat, Changsha, Hunan, Peoples R China Natl Clin Res Ctr Mental Disorders, Changsha, Hunan, Peoples R China Natl Technol Inst Mental Disorders, Changsha, Hunan, Peoples R China Hunan Key Lab Psychiat & Mental Hlth, Changsha, Hunan, Peoples R China Cent South Univ, Mental Hlth Inst, Changsha, Hunan, Peoples R China Hunan Med Ctr Mental Hlth, Changsha, Hunan, Peoples R China Jinhua Second Hosp, Jinhua, Zhejiang, Peoples R China Wenzhou Med Univ, Dept Psychiat, Affiliated Kangning Hosp, Wenzhou, Zhejiang, Peoples R China Hangzhou Seventh Peoples Hosp, Hangzhou, Zhejiang, Peoples R China Kunming Med Univ, Dept Psychiat, Affiliated Hosp 1, Kunming, Yunnan, Peoples R China Tianjin Med Univ, Nankai Univ Affiliated Tianjin Anding Hosp, Mental Hlth Teaching Hosp, Tianjin Mental Hlth Ctr, Tianjin, Peoples R China Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China Wuhan Univ, Renmin Hosp, Dept Psychiat, Wuhan, Hubei, Peoples R China Zhejiang Univ, Affiliated Hosp 1, Dept Psychiat, Sch Med, Hangzhou, Zhejiang, Peoples R China Key Lab Mental Disorder Management Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China Chinese Acad Sci, Kunming Inst Zool Chinese Univ Hong Kong KIZ CUHK, Kunming Inst Zool, Kunming, Yunnan, Peoples R China Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai, Peoples R China Peking Univ Sixth Hosp, Inst Mental Hlth, Beijing, Peoples R China Peking Univ, Natl Hlth Commiss NHC Key Lab Mental Hlth, Beijing, Peoples R China Peking Univ Sixth Hosp, Natl Clin Res Ctr Mental Disorders, Beijing, Peoples R China Peking Univ, Peking Tsinghua Joint Ctr Life Sci & Peking Univ, Beijing, Peoples R China Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming, Yunnan, Peoples R China |
| Keywords | DENDRITIC SPINE PATHOLOGY TRANSMEMBRANE PROTEIN 108 COMMON VARIANTS IDENTIFIES 2 EXPRESSION SCHIZOPHRENIA POLYGENICITY BEHAVIOR VRK2 MICE |
| Issue Date | Dec-2020 |
| Publisher | JAMA PSYCHIATRY |
| Abstract | This genome-wide association study and trans-ancestry meta-analysis explores the genetic basis of bipolar disorder in a Han Chinese population and assesses shared bipolar disorder genetic risk between Han Chinese and European populations. Importance The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood. Objective To explore the genetic basis of BD in the Han Chinese population. Design, Setting, and Participants A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020. Main Outcomes and Measures Single-nucleotide variations with P < 5.00 x 10(-8) were considered to show genome-wide significance of statistical association. Results The Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 x 10(-8); odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (rho(ge) = 0.652, SE = 0.106; P = 7.30 x 10(-10)) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R-2 = 1.27%; P = 1.30 x 10(-19)) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 x 10(-9); OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 x 10(-8); OR, 0.932; 95% CI, 0.909-0.956). Conclusions and Relevance This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis. Question What is the genetic architecture of bipolar disorder (BD) in the Han Chinese population? Findings In this genome-wide association study of 6472 individuals of Han Chinese ancestry (1822 cases and 4650 controls), several novel risk loci for BD were found, and trans-ancestry genetic correlation estimation and polygenic risk score analyses of Han Chinese and European individuals suggested a shared genetic risk of BD. Meaning Findings of this study highlighted novel genome-wide significant risk loci for BD that can provide insight into the genetic architecture of this disorder. |
| URI | http://hdl.handle.net/20.500.11897/608164 |
| ISSN | 2168-622X |
| DOI | 10.1001/jamapsychiatry.2020.3738 |
| Indexed | SCI(E) SSCI |
| Appears in Collections: | 第六医院 生命科学学院 |
