Work

Deciphering the genetic basis of electrolyte homeostasis: genome-wide association studies of plasma sodium, chloride, and potassium in two European cohorts

Year: 2026

Type: article

Abstract: BACKGROUND AND HYPOTHESIS: Chloride, potassium, and sodium are fundamental electrolytes involved in key kidney physiological processes. Previous studies focusing on the genetics of electrolyte homeostasis have mainly investigated their urinary concentrations. To date, only a few studies have investigated the genetic factors influencing the differences in plasma levels of electrolytes in the general population. METHODS: In this study, we performed genome-wide association studies (GWAS) followed by meta-analyses and post-GWAS computational investigations on the circulating levels of these electrolytes in two European cohorts, the INCIPE and the Rotterdam Study (overall n = 9 256). RESULTS: We identified 11 significant variants in 8 independent loci surpassing the genome-wide significance threshold (P < 5 × 10-8) for chloride, along with 88, 21, and 24 genomic loci suggestively associated (P < 1 × 10-5) with sodium, chloride, and potassium levels, respectively. Post-GWAS computational analyses on associated genes and variants suggested differential regulation of gene expression in heart, muscle, and kidney tissues, as well as enrichment for gene sets related to positional, transcription factor target and cell type signatures. CONCLUSIONS: The findings of this study highlight a significant genetic contribution to the homeostasis of plasma chloride, potassium, and sodium concentrations, and confirm that these electrolytes are involved not only in kidney physiology but also in broader biological processes and complex systemic interactions in the human body.

Source: Nephrology Dialysis Transplantation

DOI: 10.1093/ndt/gfag069