Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus Erythematosus
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 associati...
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doaj-8343c43f2d414acb80b9cc0f9e8cbe7d2020-11-25T03:10:17ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-07-011110.3389/fgene.2020.00600533757Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus ErythematosusFeixia Zhang0Yong-Fei Wang1Yong-Fei Wang2Yan Zhang3Zhiming Lin4Yujie Cao5Huoru Zhang6Zhong-Yi Liu7David L. Morris8Yujun Sheng9Yong Cui10Xuejun Zhang11Timothy J. Vyse12Yu Lung Lau13Wanling Yang14Yanhui Chen15Department of Pediatrics, Union Hospital Affiliated to Fujian Medical University, Fuzhou, ChinaDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong KongShenzhen Futian Hospital for Rheumatic Disease, Shenzhen, ChinaDepartment of Pediatric Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou, ChinaDepartment of Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong KongDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong KongDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong KongDivision of Genetics and Molecular Medicine, King’s College London, London, United KingdomDepartment of Dermatology, No.1 Hospital Affiliated to Anhui Medical University, Hefei, ChinaDepartment of Dermatology, No.1 Hospital Affiliated to Anhui Medical University, Hefei, ChinaDepartment of Dermatology, No.1 Hospital Affiliated to Anhui Medical University, Hefei, ChinaDivision of Genetics and Molecular Medicine, King’s College London, London, United KingdomDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong KongDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong KongDepartment of Pediatrics, Union Hospital Affiliated to Fujian Medical University, Fuzhou, ChinaSystemic 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.https://www.frontiersin.org/article/10.3389/fgene.2020.00600/fullgenome-wide association studyreplicationIRF3systemic lupus erythematosuslupus nephritis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Feixia Zhang Yong-Fei Wang 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 |
spellingShingle |
Feixia Zhang Yong-Fei Wang 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 Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus Erythematosus Frontiers in Genetics genome-wide association study replication IRF3 systemic lupus erythematosus lupus nephritis |
author_facet |
Feixia Zhang Yong-Fei Wang 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 |
author_sort |
Feixia Zhang |
title |
Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus Erythematosus |
title_short |
Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus Erythematosus |
title_full |
Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus Erythematosus |
title_fullStr |
Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus Erythematosus |
title_full_unstemmed |
Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus Erythematosus |
title_sort |
independent replication on genome-wide association study signals identifies irf3 as a novel locus for systemic lupus erythematosus |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2020-07-01 |
description |
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. |
topic |
genome-wide association study replication IRF3 systemic lupus erythematosus lupus nephritis |
url |
https://www.frontiersin.org/article/10.3389/fgene.2020.00600/full |
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