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

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Feixia Zhang, Yong Fei Wang, Yan Zhang, Zhiming Lin, Yujie Cao, Huoru Zhang, Zhong Yi Liu, David L. Morris, Yujun Sheng, Yong Cui, Xuejun Zhang, Timothy J. Vyse, Yu Lung Lau, Wanling Yang, Yanhui Chen

Original languageEnglish
Article number600
JournalFrontiers in Genetics
Published3 Jul 2020

King's Authors


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 in IRF3 (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.

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