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.
CITATION STYLE
Zhang, H., Zhang, Y., Wang, Y. F., Morris, D., Hirankarn, N., Sheng, Y., … Yang, W. (2018). Meta-analysis of GWAS on both Chinese and European populations identifies GPR173 as a novel X chromosome susceptibility gene for SLE. Arthritis Research and Therapy, 20(1). https://doi.org/10.1186/s13075-018-1590-3
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