Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals

全基因组关联研究 双相情感障碍 汉族 单核苷酸多态性 精神分裂症(面向对象编程) 基因型 医学 遗传学 人口 精神科 生物 心情 基因 环境卫生
作者
Huijuan Li,Chen Zhang,Hui Li,Dongsheng Zhou,Yi Li,Chuyi Zhang,Chuang Wang,Lu Wang,Wenqiang Li,Yongfeng Yang,Na Qu,Jinsong Tang,Ying Hé,Jun Zhou,Zihao Yang,Xingxing Li,Jun Cai,Lu Yang,Jun Chen,Weixing Fan,Wei Tang,Wenxin Tang,Qi Jia,Weiqing Liu,Chuanjun Zhuo,Xueqin Song,Fang Liu,Yan Bai,Bao‐Liang Zhong,Shufang Zhang,Jing Chen,Bin Xia,Luxian Lv,Zhongchun Liu,Shaohua Hu,Xiaoyan Li,Jie-wei Liu,Xin Cai,Yong-Gang Yao,Yuyanan Zhang,Hao Yan,Suhua Chang,Jingping Zhao,Weihua Yue,Xiong-Jian Luo,Xiaogang Chen,Xiao Xiao,Yiru Fang,Ming Li
出处
期刊:JAMA Psychiatry [American Medical Association]
卷期号:78 (3): 320-320 被引量:35
标识
DOI:10.1001/jamapsychiatry.2020.3738
摘要

The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood.To explore the genetic basis of BD in the Han Chinese population.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.Single-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association.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 × 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 (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 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 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956).This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.
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