Background: Premature arterial stiffening is a predictor of increased cardiovascular risk. It is highly heritable, but the precise molecular pathways regulating it are poorly understood. We aimed to identify genetic risk loci associated with aortic stiffness in young healthy adults (<25 years) at low cardiovascular risk.Methods: Demographic, blood pressure and aortic pulse wave velocity (aPWV) data were recorded using validated methods. Genotyping performed in ACCT individuals at the extremes (high and low aPWV, n=1200) using Illumina 610K Quad beadchip. Top 15 genome-wide (GW) signals (p<10-8<10-6) were validated in aged matched internal (n=910), ALSPAC (n=3902) and Hyderabad (n=700) study subjects. ABI Taqman and Sequenom genotyping assays were used for replication. SNPs were also tested for their association with aPWV after adjusting for covariates. Data was analysed using PLINK and multiple regression analyses.Results: In primary analysis, 7 SNPs reached GW significance (p<10-8), 20 had threshold of p<10-7p<10-6 and 112 had nominal value of 10-5. Top 7 SNPs had β values ranging from 0.38 to 0.17 per allele and overall explained just under 5% of total variance in ACCT. Figure illustrates the regional association plot for chromosome 6, which shows a number of SNPs around the strongest signal from rs6932930. Of 15 SNPs validated, 5 were successfully replicated in ALSPAC, Hyderabad cohorts and 3 in internal sample (p<0.05).Conclusions: Multiple loci are associated with premature large artery stiffening in both ACCT and replication cohorts. Additional studies are needed to understand the biological pathways/mechanisms involved.
Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCA193
Poster Communications: Genome wide scan for arterial stiffness identifies loci associated with aortic pulse wave velocity
Y. Yasmin1, C. McEniery1, S. Cleary1, B. Lam2, H. Kuper3, Y. Endo1, S. Kinra3, D. Chen1, G. Chandak4, J. Cockcroft5, J. Deanfield6, D. Lawlor7, I. Wilkinson1, K. O'Shaughnessy1
1. Medicine, University of Cambridge, Cambridge, United Kingdom. 2. Insttitute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom. 3. London School of Hygiene & Tropical Medicine, London, United Kingdom. 4. Centre for Cellular & Molecular Biology, Hyderabad, India. 5. Cardiology, Cardiff University, Cardiff, United Kingdom. 6. National Centre for Cardiovascular Prevention & Outcomes, University College London, London, United Kingdom. 7. School of Social & Community Medicine, Bristol University, Bristol, United Kingdom.
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.