Genome‐wide scan for arterial stiffness identifies loci associated with aortic pulse wave velocity (912.5)

• DOI: 10.1096/fasebj.28.1_supplement.912.5
• Publication Date: 2021-06-16T09:41:54Z
• Authors: Y Yasmin; C McEniery; S Cleary; B Lam; H Kuper; Y Endo; S Kinra; D Chen; G Chandak; J Cockcroft; J Deanfield; D Lawlor; I Wilkinson; K O'Shaughnessy
• Keywords: Genome-wide Association Study

Background: Premature arterial stiffening is a predictor of increased cardiovascular risk. It 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 Methods: Demographic, blood pressure and pulse wave velocity (aPWV) data were recorded using validated methods. Genotyping performed ACCT individuals extremes (high aPWV, n=1200) Illumina 610K Quad beadchip. Top 15 genome-wide (GW) signals (p<10-8<10-6) aged matched internal (n=910), ALSPAC (n=3902) Hyderabad (n=700) study subjects. ABI Taqman Sequenom genotyping assays used for replication. SNPs also tested their association aPWV after adjusting covariates. Results: In primary analysis, 7 reached GW significance (p<10-8), 20 had threshold p<10-7p<10-6 112 nominal value 10-5. β values ranging from 0.38 0.17 per allele overall explained just under 5% total variance ACCT. Adjacent regional plot chromosome 6, shows number around strongest signal rs6932930. Of validated, 5 successfully replicated ALSPAC, cohorts 3 sample (p<0.05). Conclusions: Multiple premature large artery both replication cohorts. Additional studies needed understand biological pathways/mechanisms involved. Grant Funding Source: British Heart Foundation