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

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

doi:10.3389/fgene.2020.00600

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

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^*

^*Corresponding author for this work

Medical & Molecular Genetics

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

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.

Original language	English
Article number	600
Journal	Frontiers in Genetics
Volume	11
DOIs	https://doi.org/10.3389/fgene.2020.00600
Publication status	Published - 3 Jul 2020

Keywords

genome-wide association study
IRF3
lupus nephritis
replication
systemic lupus erythematosus

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Zhang, F., Wang, Y. F., Zhang, Y., Lin, Z., Cao, Y., Zhang, H., Liu, Z. Y., Morris, D. L., Sheng, Y., Cui, Y., Zhang, X., Vyse, T. J., Lau, Y. L., Yang, W., & Chen, Y. (2020). Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus Erythematosus. Frontiers in Genetics, 11, Article 600. https://doi.org/10.3389/fgene.2020.00600

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

abstract = "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.",

keywords = "genome-wide association study, IRF3, lupus nephritis, replication, systemic lupus erythematosus",

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

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T1 - Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus Erythematosus

AU - Zhang, Feixia

AU - Wang, Yong Fei

AU - Zhang, Yan

AU - Lin, Zhiming

AU - Cao, Yujie

AU - Zhang, Huoru

AU - Liu, Zhong Yi

AU - Morris, David L.

AU - Sheng, Yujun

AU - Cui, Yong

AU - Zhang, Xuejun

AU - Vyse, Timothy J.

AU - Lau, Yu Lung

AU - Yang, Wanling

AU - Chen, Yanhui

PY - 2020/7/3

Y1 - 2020/7/3

N2 - 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.

AB - 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.

KW - genome-wide association study

KW - IRF3

KW - lupus nephritis

KW - replication

KW - systemic lupus erythematosus

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JF - Frontiers in Genetics

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ER -

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

Abstract

Keywords

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