Effects of 25-Hydroxyvitamin D Levels on Renal Function: A Bidirectional Mendelian Randomization Study
Authors' conclusion
Genetically predicted CKD, increased BUN, and decreased eGFR are associated with increased 25(OH)D levels, but we found no causal effect of 25(OH)D on renal function in Europeans.
Study context
- Population
- Europeans: Single nucleotide polymorphisms (SNPs) for 25(OH)D from 443,734 individuals; GWAS of renal function totaling over 1 million25(OH)D GWAS
- Participants
- 443,734 participants
- Comparison
- Genetically predicted 25D vs renal function, and the reverse
- Outcome
- Causal effect of 25(OH)D on eGFR, BUN, CKD risk and progression, and of renal function on 25(OH)D
Methodological detailsbidirectional (reverse Mendelian randomization (MR)), gene-restricted SNP analysis (DHCR7, CYP2R1, GC) to control pleiotropy
- Bidirectional (reverse MR)
- Gene-restricted SNP analysis (DHCR7, CYP2R1, GC) to control pleiotropy
Main finding
As reported in the abstract
Effect of 25(OH)D on renal function
- No robust evidence of effects of 25(OH)D on estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and chronic kidney disease (CKD) or its progression
Further findings
Reverse MR: eGFR on standardized log-transformed 25(OH)D (per unit increase in log-transformed eGFR)
- Decrease in standardized log-transformed 25(OH)D
- 0.56 (95% CI −0.73, −0.41; P = 2.89 × 10-12)
- Inverse variance weighted MR
Reverse MR: BUN on 25(OH)D (per unit increase in log-transformed BUN)
- β for increased 25(OH)D
- 0.25 (95% CI 0.15, 0.36; P = 4.12 × 10-6)
Reverse MR: genetically predicted CKD on standardized log-transformed 25(OH)D
- Increase in standardized log-transformed 25(OH)D
- 0.05 (95% CI 0.04, 0.06; P = 1.06 × 10-13)
- Other MR methods confirmed the findings
Original publication
Effects of 25-Hydroxyvitamin D Levels on Renal Function: A Bidirectional Mendelian Randomization Study. J Clin Endocrinol Metab. Published 13 December 2022. doi:10.
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