Two-sample mendelian randomization study: vitamin D levels and chronic kidney disease in the elderly population

Objective: To investigate whether there was a causal relationship between serum vitamin D levels and chronic kidney disease (CKD), specifically focusing on estimated glomerular filtration rate (eGFR) and CKD stages, in the elderly population (aged 60 and above). Participants: UK Biobank data were utilized for Genome-wide association study (GWAS) of serum vitamin D levels, involving 327,657 elderly participants. CKDGen Consortium were employed for kidney outcomes, including 133,814 participants for eGFR analysis and 117,165 participants for CKD stages G3-G5 analysis, predominantly involving elderly individuals of European ancestry from various countries. Methods: GWAS was performed to identify single nucleotide polymorphisms (SNPs) associated with vitamin D levels in UK Biobank. Based on these SNPs, Mendelian randomization (MR) analyses were conducted between vitamin D levels and kidney outcomes (eGFR and CKD stages G3-G5) in CKDGen Consortium. Results: 553 SNPs were found associated with vitamin D levels (p < 5 × 10 −8 ), 17 of which were independent and available in CKDGen. We did not find robust evidence supporting effects of vitamin D levels on eGFR (OR = 0.9684, 95% CI: 0.9368-1.0081, p = 0.06080) or CKD stages G3-G5 diagnosis (OR = 1.0177, 95% CI: 0.8048-1.2043, p = 0.60399) in the elderly population. Extensive sensitivity analyses corroborated these findings, further reinforcing the lack of significant casual impact of vitamin D levels on renal outcomes in the elderly population. Conclusion: The present MR study indicated that vitamin D levels were unlikely to play a significant causal role in affecting eGFR or CKD stages in the elderly population. Keywords: Mendelian Randomization, elderly population, vitamin D, chronic kidney disease, glomerular filtration rate