Proteome-Wide Genetic Investigation of Large Artery Stiffness.

The molecular mechanisms contributing to large artery stiffness (LAS) are not fully understood. The aim of this study was to investigate the association between circulating plasma proteins and LAS using complementary proteomic and genomic analyses. A total of 106 proteins associated with carotid-femoral pulse-wave velocity, a noninvasive measure of LAS, were identified in 1,178 individuals from the Asklepios study cohort. Mendelian randomization analyses revealed causal effects of 13 genetically predicted plasma proteins on pulse pressure, including cartilage intermediate layer protein-2, high-temperature requirement A serine peptidase-1, and neuronal growth factor-1. These findings suggest potential novel therapeutic targets to reduce LAS and its related diseases.