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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

Arthritis Research & Therapy 1/2018

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

Zeitschrift:
Arthritis Research & Therapy > Ausgabe 1/2018
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s13075-018-1590-3) contains supplementary material, which is available to authorized users.
Huoru Zhang and Yan Zhang contributed equally to this work.

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 (Pmeta = 7.53 × 10− 9, ORmeta= 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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