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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.    Electronic supplementary material  The online version of this article (10.1186/s13075-018-1590-3) contains supplementary material, which is available to authorized users.

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