Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus Erythematosus

被引：13

作者：

Zhang, Feixia ^{[1
]}

Wang, Yong-Fei ^{[2
,3
]}

Zhang, Yan ^{[4
]}

Lin, Zhiming ^{[5
]}

Cao, Yujie ^{[2
]}

Zhang, Huoru ^{[2
]}

Liu, Zhong-Yi ^{[2
]}

Morris, David L. ^{[6
]}

Sheng, Yujun ^{[7
]}

Cui, Yong ^{[7
]}

Zhang, Xuejun ^{[7
]}

Vyse, Timothy J. ^{[6
]}

Lau, Yu Lung ^{[2
]}

Yang, Wanling ^{[2
]}

Chen, Yanhui ^{[1
]}

机构：

[1] Fujian Med Univ, Dept Pediat, Union Hosp, Fuzhou, Peoples R China

[2] Univ Hong Kong, Dept Paediat & Adolescent Med, Hong Kong, Peoples R China

[3] Shenzhen Futian Hosp Rheumat Dis, Shenzhen, Peoples R China

[4] Guangzhou Women & Childrens Med Ctr, Dept Pediat Surg, Guangzhou, Peoples R China

[5] Sun Yat Sen Univ, Dept Rheumatol, Affiliated Hosp 3, Guangzhou, Peoples R China

[6] Kings Coll London, Div Genet & Mol Med, London, England

[7] Anhui Med Univ, Dept Dermatol, 1 Hosp, Hefei, Peoples R China

来源：

FRONTIERS IN GENETICS | 2020年 / 11卷

基金：

中国国家自然科学基金;

关键词：

genome-wide association study; replication; IRF3; systemic lupus erythematosus; lupus nephritis; INTERFERON REGULATORY FACTOR-3; GENETIC ASSOCIATION; METAANALYSIS; PATHOGENESIS; CHINESE; IFIH1; AUTOIMMUNITY; INDIVIDUALS; VARIANTS; INNATE;

D O I：

10.3389/fgene.2020.00600

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Systemic lupus erythematosus (SLE) is a genetically complex autoimmune disease. Despite the significant progress made in identifying susceptibility genes for SLE, the genetic architecture of the disease is far from being understood. In this study, we set to replicate a number of suggestive association signals found in genome-wide association studies (GWASs) in additional independent cohorts. Replication studies were performed on Han Chinese cohorts from Hong Kong and Anhui, involving a total of 2,269 cases and 5,073 controls. We identified a missense variant inIRF3(rs7251) reaching genome-wide significance through a joint analysis of GWAS and replication data (OR = 0.876, P = 4.40E-08). A significant correlation was observed between rs7251 and lupus nephritis (LN) by subphenotype stratification (OR = 0.785, P = 0.0128). IRF3 is a key molecule in type I interferon production upon nucleic acid antigen stimulations and may inhibit regulatory T cell differentiation. Further elucidation of the mechanism of this association could help us better understand the pathogenesis of SLE.

引用

页数：7

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