Kidney stone disease (KSD) is a complex disorder with high heritability and prevalence. We performed a large genome-wide association study (GWAS) meta-analysis for KSD to date, including 720,199 individuals with 17,969 cases in European population. We identified 44 susceptibility loci, including 28 novel loci. Cell type-specific analysis pinpointed the proximal tubule as the most relevant cells where susceptibility variants might act through a tissue-specific fashion. By integrating kidney-specific omics data, we prioritized 223 genes which strengthened the importance of ion homeostasis, including calcium and magnesium in stone formation, and suggested potential target drugs for the treatment. The genitourinary and digestive diseases showed stronger genetic correlations with KSD. In this study, we generate an atlas of candidate genes, tissue and cell types involved in the formation of KSD. In addition, we provide potential drug targets for KSD treatment and insights into shared regulation with other diseases.
Nature communications. 2023 Nov 18*** epublish ***
Xingjie Hao, Zhonghe Shao, Ning Zhang, Minghui Jiang, Xi Cao, Si Li, Yunlong Guan, Chaolong Wang
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. ., Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China., Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China., Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. .