Genetic variants predisposing to an increased risk of kidney stone disease.

ABSTRACT: BACKGROUNDKidney stone disease (KSD) affects approximately 10% of adults, is heritable, and is associated with mineral metabolic abnormalities.METHODSGenetic variants and pathways increasing KSD risk via calcium and phosphate homeostasis were ascertained using GWAS, region-specific Mendelian randomization (MR), and genetic colocalization. The utility of pathway modulation was estimated via drug target MR, and the effects of variants on calcium-sensing receptor (CaSR) signaling were characterized.RESULTSSeventy-nine independent KSD-associated genetic signals at 71 loci were identified. MR identified 3 loci affecting KSD risk via increased serum calcium or decreased serum phosphate concentrations (ORs for genomic regions = 4.30, 11.42, and 13.83 per 1 SD alteration; P < 5.6 × 10-10). Colocal

SUBMITTER: Lovegrove CE 

PROVIDER: S-EPMC12321396 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature