Abstract MP34: Significant Associations between Genetic Variation on Chromosome 10p and Arterial Stiffness in Adults from the Fels Longitudinal Study
Arterial stiffness is associated with increased cardiovascular disease (CVD) risk. And, some recent studies have reported that arterial stiffness measures, such as pulse wave velocity (PWV), are under significant genetic control. In this study, we performed genome-wide association (GWA) analysis on arterial stiffness in a sample of 805 white adults (378 males; 427 females) aged 18-92 years from 113 families in the Fels Longitudinal Study.
Arterial stiffness was measured as brachial-ankle PWV using the Vascular Profiling System-1000 (Omron Inc., San Antonio, TX). PWV was adjusted for covariates including age, sex, height and/or mean arterial pressure, and was inverse normal transformed in the genetic analyses. Each subject was genotyped with the Illumina Human 610-Quad BeadChip containing more than 550,000 single nucleotide polymorphism (SNP) markers. GWA analyses were conducted using the measured genotype method implemented in SOLAR, allowing for residual non-independence among relatives.
PWV was significantly heritable (h2 ± SE = 0.41 ± 0.08). We observed two genome-wide significant (χ2>27.85) associations: rs11009438 (χ2=35.26, p=3.0×10-9), and rs1574514 (χ2=32.72, p=1.1×10-8), both located on chromosome 10p. For rs11009438, the minor allele (A) has a frequency of 0.14 and is associated with a 0.444 SDU increase of PWV, accounting for 4.9% of the variation in PWV. For rs1574514, the minor allele (A) has a frequency of 0.13 and is associated with a 0.428 SDU increase of PWV, accounting for 4.6% of the variation in PWV. We also observed two suggestive (χ2>22.70) associations for PWV in this same region of chromosome 10p (rs7088857 and rs2804877), as well as suggestive associations on chromosome 1p (rs12723920, rs12024171, and rs677769), and chromosome 11p (rs2224528). While no positional candidate genes are directly associated with these SNPs, it is worth noting that one gene (NRP1 on 10p12), coding for neuropilin 1, is located near (~230Kbp) our significant and suggestive associations on chromosome 10p. NRP1 has been associated with angiogenesis and vasodilatation through its interaction with vascular endothelial growth factors.
In summary, we identified several SNPs significantly or suggestively associated with arterial stiffness as measured by PWV. Future work will include replication of these results in other study populations, and examining shared genetic influences on arterial stiffness and other CVD risk factors.
- © 2013 by American Heart Association, Inc.