Abstract: PO0344
Genetic Determinants of Circulating Fibroblast Growth Factor 23 and Risk of Coronary Artery Disease
Session Information
- Biochemical Aspects of Mineral and Bone Disease
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Pike, Mindy, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Akwo, Elvis A., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Lipworth, Loren, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Hung, Adriana, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
Observational studies suggest that elevated levels of circulating fibroblast growth factor-23 (FGF-23) contribute to the burden of cardiovascular disease, in the setting of chronic kidney disease and in the general population. These studies can suffer from confounding and reverse causation, limiting their ability to identify causal associations. Mendelian randomization (MR) has emerged as a powerful study design to provide evidence supporting or refuting causality by utilizing the genetic determinants of a risk factor. We used MR to evaluate whether genetically predicted higher FGF-23 levels are associated with the risk of coronary artery disease (CAD).
Methods
We performed two-sample MR of the relationship between FGF-23 and CAD with the use of summary statistics from the CARDIoGRAMplusC4D consortium's genome-wide association meta-analysis of 48 studies with a total of 60,801 CAD cases and 123,504 non-cases. We selected 5 single nucleotide polymorphisms (SNPs) robustly associated with FGF-23 at genome-wide significance among 16,624 individuals as instrumental variables.
Results
A genetic predisposition to higher FGF-23 levels was associated with CAD. In conventional MR analysis, the odds ratio of CAD was 1.44 (95% confidence interval 1.14 to 1.7, p=0.03) per 10-fold increase in genetically predicted FGF-23 levels. Results were consistent in sensitivity analyses using the weighted median and heterogeneity-penalized model averaging methods.
Conclusion
This study provides evidence that FGF-23 levels are causally associated with risk of CAD. Whether interventions to lower FGF-23 result in decreased risk of CAD remains to be determined but warrants investigation.
Funding
- NIDDK Support