Abstract Body (Do not enter title and authors here): Background: Arterial stiffness serves as an independent predictor of cardiovascular disease risk. Pulse-wave velocity (PWV) is a non-invasive measurement of arterial stiffness. However, the genetic risk variants associated with arterial stiffness in the Asian ancestry population remain largely unknown. This lack of knowledge hinders the development of targeted preventive and treatment strategies.
Hypothesis: Arterial stiffness is associated with genotyped SNP loci that have genetic relationships with metabolic syndrome phenotypes.
Methods: For PWV, we performed genome-wide association study and gene-based genetic association study in 912 individuals from the Tongji-BGI research cardiovascular health (TORCH) cohort. We then used linkage disequilibrium score regression to estimate pairwise genetic correlations between arterial stiffness, blood pressure, lipids, and diabetes.
Results: Eleven risk loci associated with arterial stiffness were discovered at genome-wide significance (P < 5 × 10⁻⁸), including three in intronic (rs978453410 mapping to PPP2R5E; rs146270927 mapping to ECI1; rs189517402 mapping to CNN2 ). UBE2U and ECI1 were identified as the PWV-associated genes by gene-based analysis. Genetic correlation analyses revealed inter-related of PWV with systolic blood pressure, mean arterial pressure, total cholesterol and diabetes.
Conclusions: This research firstly identified eleven novel genetic variants associated with arterial stiffness in Asian ancestry individuals. Further research aimed at reducing arterial stiffness may benefit from the identification of SNPs and genes like ECI1, which is related to the oxidation of unsaturated fatty acids in the mitochondria.