Background: Nephrolithiasis is a significant global health and economic challenge, with an increasing prevalence and a high recurrence rate. However, there is limited knowledge regarding the potential associations between calcium nephrolithiasis risk and Chinese Han populations currently. Methods: To identify the genetic factors for calcium nephrolithiasis, we presented a genome-wide association study (GWAS) using a total of 1006 calcium nephrolithiasis cases and 1200 controls of Chinese Han ethnicity. Suggestive loci (p < 1.0 × 10−6) were replicated in 445 cases and 1008 controls. We also assessed the association of GWAS-level significant single-nucleotide polymorphisms (SNPs) with quantitative traits, including metabolic, kidney-related, and electrolyte traits. Results: Here we found three novel loci for calcium nephrolithiasis: SORBS2 on 4q35.1 (rs3736194; p = 2.84 × 10−13, OR = 0.6279), CXXC5 on 5q31.2 (rs356450; p = 6.09 × 10−16, OR = 2.0312), and MBD2 on 18q21.21 (rs55826947; p = 6.29 × 10−10, OR = 0.6017). Subsequent analyses revealed the association of SNP rs3736194 with higher serum carbon dioxide (p = 0.04666), rs356450 with lower serum chloride (p = 0.02992), and rs55826947 with higher BMI (p = 0.03174), respectively. Conclusions: We performed the first GWAS on calcium nephrolithiasis in a Chinese Han population cohort and identified three novel susceptibility loci on 4q35.1, 5q31.2, and 18q21.2. Further research into the molecular mechanisms underlying these variations in nephrolithiasis is warranted.
Wang et al. (Tue,) studied this question.