Identification of End Stage Renal Disease Associated Loci in X Chromosome: an X Chromosome-Wide Association Study

Background X-chromosomal genetic variants have been understudied in end stage renal disease (ESRD), which hold the promise to provide valuable insights into sexually dimorphic traits and diseases. Methods We performed a X chromosome-wide association study (XWAS) in a Chinese cohort (N = 2750), comprising 1489 cases with ESRD and 1261 controls, to identify locus associated with ESRD risk. Results One sex-shared loci, rs3138874 located in the promoter of COL4A5 were identified in the meta-analysis on the summary statistics from the sex-stratified XWAS. Additionally, 2 male-specific loci, comprising rs142591759 near MIR3202-2 and rs73250616 near SYTL4 were identified in the sex-stratified XWAS in males. Of the 3 ESRD associated loci, 2 were previously found to be associated with estimated Glomerular filtration rate (eGFR) in different populations. Finally, by integrating expression quantitative trait loci (eQTL) statistics from multiple tissues and conducting eQTL colocalization analysis, we found that SYTL4, TSPAN6, NOX1, CSTF2, PCDH19 and RPL36A are the target genes of ESRD associated locus Xq22.1. Conclusion Our finding revealed three X-chromosome loci linked to ESRD risk, which provided foundational knowledge for genetic risk prediction and advanced our understanding of the molecular underpinnings of ESRD.