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

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

JOURNAL=Frontiers in Genetics

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00600

DOI=10.3389/fgene.2020.00600

ISSN=1664-8021

ABSTRACT=Systemic lupus erythematosus (SLE) is a genetically complex autoimmune disease. Despite significant progresses in identifying susceptibility genes for SLE, the genetic architecture of the disease is far from understood. In this study, we set to replicate a number of suggestive association signals found in genome-wide association studies (GWAS) in additional independent cohorts. Replication studies were performed on Han Chinese cohorts from Hong Kong and Anhui, involving a total of 2269 cases and 5073 controls. We identified a missense variant in IRF3 (rs7251) reaching genome-wide significance by joint analysis of GWAS and replication data (OR=0.876, P=4.40E-08). 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.