Genetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study.

introductionFibroblast growth factor 23 (FGF23), a potential biomarker for kidney function, is related to cardiovascular disease (CVD) and diabetes, although it is unclear whether the relation is causal. This study evaluated the associations of genetically predicted FGF23 with major CVDs, their risk factors, kidney function, and longevity using Mendelian randomization (MR).

methodsThis is a two-sample MR study using summary statistics from large genome-wide association studies. Primary outcomes included coronary artery disease (CAD), myocardial infarction, heart failure, and atrial fibrillation. Secondary outcomes included cardiovascular risk factors, kidney function, and longevity. We used four single-nucleotide polymorphisms (SNPs) predicting FGF23, excluding rs2769071 in the

resultsUsing IVW, genetically predicted higher FGF23 was inversely associated with risk of CAD [odds ratio (OR): 0.69 per logtransformed FGF23 (pg/ml) increase, 95% confidence interval (CI): 0.52-0.91] and type 2 diabetes mellitus (T2DM) (OR: 0.70, 95% CI: 0.52-0.96), but not with the other outcomes. The WM and MR-Egger estimates were directionally consistent.

conclusionThis study suggests that genetically predicted higher FGF23 may be protective against CAD and T2DM. Future studies should explore the underlying mechanisms related to the potential protective effect of FGF23. FGF23 was unlikely a cause of poorer renal function.