# A Genome-Wide Association Study on Calcium Nephrolithiasis in Chinese Han Population Identifies Novel Susceptible Loci at 4q35.1, 5q31.2 and 18q21.2

## TL;DR

This study identifies three new genetic loci linked to calcium kidney stones in the Chinese Han population, offering insights into the genetic basis of the condition.

## Contribution

The study is the first genome-wide association study on calcium nephrolithiasis in the Chinese Han population, identifying three novel susceptibility loci.

## Key findings

- Three novel loci (SORBS2, CXXC5, MBD2) were found to be significantly associated with calcium nephrolithiasis in the Chinese Han population.
- Each identified SNP showed associations with specific metabolic or kidney-related traits, such as serum chloride and BMI.
- The study provides a foundation for future research into the molecular mechanisms of nephrolithiasis in this population.

## Abstract

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.