Serum Parathyroid Hormone and Risk of Coronary Artery Disease: Exploring Causality Using Mendelian Randomization.

Abstract

Elevated circulating parathyroid hormone concentrations have been associated with increased risk of cardiovascular disease in observational studies, but whether the association is causal is unknown. We used the Mendelian randomization design to test whether genetically increased serum parathyroid hormone (S-PTH) concentrations are associated with coronary artery disease (CAD). Five single-nucleotide polymorphisms robustly associated with S-PTH concentrations were used as instrumental variables to estimate the association of genetically higher S-PTH concentrations with CAD. Summary statistics data for CAD were obtained from a genetic consortium with data from 184,305 individuals (60,801 CAD cases and 123,504 noncases). OR of CAD per genetically predicted one SD increase of S-PTH concentrations. Genetically higher S-PTH concentration was not associated with CAD as a whole or myocardial infarction specifically (∼70% of total cases). The ORs per genetically predicted one SD increase in S-PTH concentration were 1.01 (95% CI: 0.93 to 1.09; P = 0.88) for CAD and 1.02 (95% CI: 0.94 to 1.10; P = 0.64) for myocardial infarction. The lack of association remained in various sensitivity analyses. Genetic predisposition to higher S-PTH concentrations does not appear to be an independent risk factor for CAD.