BACKGROUND AND PURPOSE: Identification of subclinical atherosclerosis by ultrasonographic measurement of carotid intima-media thickness (IMT) is a validated tool, in conjunction with traditional risk factors, for clinical assessment of cardiovascular disease risk. IMT has also been recognized as a quantitative measure of cardiovascular disease progression in asymptomatic individuals, and many candidate gene association studies have attempted to identify genetic variants associated with interindividual differences in IMT with limited success. We sought to test the association between subclinical atherosclerosis measured by IMT and approximately 50,000 SNPs, densely mapping approximately 2100 genes found on the gene-centric Illumina cardiovascular disease beadchip in a multi-ethnic population-based sample. METHODS: IMT was measured by B-mode ultrasound and DNA was collected from a population-based sample of South Asian (n=328), Chinese (n=302), and European Caucasian (n=268) participants. Genetic association was measured using multivariate linear regression including adjustment for covariates. RESULTS: The most robust association across all models tested was observed for a SNP (rs3791398) in histone deacetylase 4 (HDAC4; P=1.8e-5 to P=3.6e-5), while another strong association signal was observed with natriuretic peptide receptor a/guanylate cyclase A (NPR1) (rs10082235, P=5.4e-5). Seven of 13 previously reported functional candidate genes contained a SNP that was marginally associated (0.01 < P < or = 0.05). CONCLUSION: This initial multi-ethnic high-density association study of carotid IMT suggests some novel loci requiring further evaluation in follow-up studies.
BACKGROUND AND PURPOSE: Identification of subclinical atherosclerosis by ultrasonographic measurement of carotid intima-media thickness (IMT) is a validated tool, in conjunction with traditional risk factors, for clinical assessment of cardiovascular disease risk. IMT has also been recognized as a quantitative measure of cardiovascular disease progression in asymptomatic individuals, and many candidate gene association studies have attempted to identify genetic variants associated with interindividual differences in IMT with limited success. We sought to test the association between subclinical atherosclerosis measured by IMT and approximately 50,000 SNPs, densely mapping approximately 2100 genes found on the gene-centric Illumina cardiovascular disease beadchip in a multi-ethnic population-based sample. METHODS: IMT was measured by B-mode ultrasound and DNA was collected from a population-based sample of South Asian (n=328), Chinese (n=302), and European Caucasian (n=268) participants. Genetic association was measured using multivariate linear regression including adjustment for covariates. RESULTS: The most robust association across all models tested was observed for a SNP (rs3791398) in histone deacetylase 4 (HDAC4; P=1.8e-5 to P=3.6e-5), while another strong association signal was observed with natriuretic peptide receptor a/guanylate cyclase A (NPR1) (rs10082235, P=5.4e-5). Seven of 13 previously reported functional candidate genes contained a SNP that was marginally associated (0.01 < P < or = 0.05). CONCLUSION: This initial multi-ethnic high-density association study of carotid IMT suggests some novel loci requiring further evaluation in follow-up studies.
Authors: Yang Chen; Ye Zheng; Seethalakshmi R Iyer; Gerald E Harders; Shuchong Pan; Horng H Chen; Tomoko Ichiki; John C Burnett; S Jeson Sangaralingham Journal: J Mol Cell Cardiol Date: 2019-04-04 Impact factor: 5.000
Authors: Phillip E Melton; Melanie A Carless; Joanne E Curran; Thomas D Dyer; Harald H H Göring; Jack W Kent; Eugene Drigalenko; Matthew P Johnson; Jean W Maccluer; Eric K Moses; Anthony G Comuzzie; Michael C Mahaney; Daniel H O'Leary; John Blangero; Laura Almasy Journal: Circ Cardiovasc Genet Date: 2013-03-13
Authors: Thahira J Rahman; Elizabeth A Walker; Bongani M Mayosi; Darroch H Hall; Peter J Avery; John M C Connell; Hugh Watkins; Paul M Stewart; Bernard Keavney Journal: PLoS One Date: 2011-08-12 Impact factor: 3.240
Authors: Thomas W Frazier; Eric A Youngstrom; Brian A Frankel; Giovana B Zunta-Soares; Marsal Sanches; Michael Escamilla; David A Nielsen; Jair C Soares Journal: Brain Behav Date: 2014-03-18 Impact factor: 2.708