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03-05-2018 | Systemic lupus erythematosus | Article

Meta-analysis of GWAS on both Chinese and European populations identifies GPR173 as a novel X chromosome susceptibility gene for SLE

Journal: Arthritis Research & Therapy

Authors: Huoru Zhang, Yan Zhang, Yong-Fei Wang, David Morris, Nattiya Hirankarn, Yujun Sheng, Jiangshan Shen, Hai-Feng Pan, Jing Yang, Sen Yang, Yong Cui, Dong-Qing Ye, Timothy J. Vyse, Xuejun Zhang, Yu Lung Lau, Wanling Yang

Publisher: BioMed Central

Abstract

Background

Systemic lupus erythematous (SLE) is a complex autoimmune disease with female predominance, particularly affecting those of childbearing age. We performed analysis of three genome-wide genotyping datasets of populations of both Chinese and European origin.

Methods

This study involved 5695 cases and 10,357 controls in the discovery stage. The lead signal on chromosome X was followed by replication in three additional Asian cohorts, with 2300 cases and 4244 controls in total. Conditional analysis of the known associated loci on chromosome X was also performed to further explore independent signals.

Results

Single-nucleotide polymorphism rs13440883 in GPR173 was found to be significantly associated with SLE (P_meta = 7.53 × 10^− 9, OR_meta= 1.16), whereas conditional analysis provided evidence of a potential independent signal in the L1CAM-IRAK1-MECP2 region in Asian populations (rs5987175 [LCA10]).

Conclusions

We identified a novel SLE susceptibility locus on the X chromosome. This finding emphasizes the importance of the X chromosome in disease pathogenesis and highlights the role of sex chromosomes in the female bias of SLE.

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