首页 / 院系成果 / 成果详情页

Systematic Integration of Brain eQTL and GWAS Identifies ZNF323 as a Novel Schizophrenia Risk Gene and Suggests Recent Positive Selection Based on Compensatory Advantage on Pulmonary Function 期刊论文

编号：

3058b4b2-c47b-4a56-93b0-972d818e21fa
作者：

Luo, XiongJian^[1];Mattheisen, Manuel^{[2,3,4,5,6,7]};Li, Ming^[8];Huang, Liang^[9];Rietschel, Marcella^[10];Borglum, Anders D.^[2,3,4,5,11];Als, Thomas D.^[2,3,4,5];van den Oord, Edwin J.^[12];Aberg, Karolina A.^[12];Mors, Ole^[4,5,13];Mortensen, Preben Bo^[4,5,14];Luo, Zhenwu^[15];Degenhardt, Franziska^[6,7];Cichon, Sven^[16,17];Schulze, Thomas G.^[18,19];Noethen, Markus M.^[6,7];Su, Bing^[20];Zhao, Zhongming^[21,22];Gan, Lin^[23,24];Yao, YongGang(姚永刚)^[1,25]
语种：

英文
期刊：

SCHIZOPHRENIA BULLETIN ISSN：0586-7614 2015 年 41 卷 6 期 (1294 - 1308) ; NOV
疾病分类：

其它感染性疾病
关键词：

schizophrenia ZNF323 association eQTL hippocampus positive selection
摘要：

Genome-wide association studies have identified multiple risk variants and loci that show robust association with schizophrenia. Nevertheless, it remains unclear how these variants confer risk to schizophrenia. In addition, the driving force that maintains the schizophrenia risk variants in human gene pool is poorly understood. To investigate whether expression-associated genetic variants contribute to schizophrenia susceptibility, we systematically integrated brain expression quantitative trait loci and genome-wide association data of schizophrenia using Sherlock, a Bayesian statistical framework. Our analyses identified ZNF323 as a schizophrenia risk gene (P = 2.22x10(-6)). Subsequent analyses confirmed the association of the ZNF323 and its expression-associated single nucleotide polymorphism rs1150711 in independent samples (gene-expression: P = 1.40x10(-6); single-marker meta-analysis in the combined discovery and replication sample comprising 44123 individuals: (P = 6.85x10(-10)). We found that the ZNF323 was significantly downregulated in hippocampus and frontal cortex of schizophrenia patients (P = .0038 and P = .0233, respectively). Evidence for pleiotropic effects was detected (association of rs1150711 with lung function and gene expression of ZNF323 in lung: P = 6.62x10(-5) and P = 9.00x10(-5), respectively) with the risk allele (T allele) for schizophrenia acting as protective allele for lung function. Subsequent population genetics analyses suggest that the risk allele (T) of rs1150711 might have undergone recent positive selection in human population. Our findings suggest that the ZNF323 is a schizophrenia susceptibility gene whose expression may influence schizophrenia risk. Our study also illustrates a possible mechanism for maintaining schizophrenia risk variants in the human gene pool.
推荐引用方式
GB/T 7714：

Luo Xiong-Jian,Mattheisen Manuel,Li Ming, et al. Systematic Integration of Brain eQTL and GWAS Identifies ZNF323 as a Novel Schizophrenia Risk Gene and Suggests Recent Positive Selection Based on Compensatory Advantage on Pulmonary Function [J].SCHIZOPHRENIA BULLETIN,2015,41(6):1294-1308.
APA：

Luo Xiong-Jian,Mattheisen Manuel,Li Ming,Huang Liang,&Yao Yong-Gang.(2015).Systematic Integration of Brain eQTL and GWAS Identifies ZNF323 as a Novel Schizophrenia Risk Gene and Suggests Recent Positive Selection Based on Compensatory Advantage on Pulmonary Function .SCHIZOPHRENIA BULLETIN,41(6):1294-1308.
MLA：

Luo Xiong-Jian, et al. "Systematic Integration of Brain eQTL and GWAS Identifies ZNF323 as a Novel Schizophrenia Risk Gene and Suggests Recent Positive Selection Based on Compensatory Advantage on Pulmonary Function" .SCHIZOPHRENIA BULLETIN 41,6(2015):1294-1308.
数据来源自科睿唯安Web of Science核心合集
入库时间：

2021/11/8 16:42:55
更新时间：

2021/11/8 16:42:55

浏览次数：20  下载次数：0

分享到：

浏览次数：20

下载次数：0

打印次数：0