Dataset Information

GWAS-identified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb.

ABSTRACT: Large-scale genome-wide association studies (GWAS) have so far identified 45 loci that are robustly associated with coronary heart disease (CHD) in data from adult men and women of European descent.To examine whether the CHD-associated loci are associated with measures of atherosclerosis in data from up to 9582 individuals of European ancestry.Forty-five SNPs representing the CHD-associated loci were genotyped in middle-aged to elderly individuals of European descent from four independent population-based studies (IMPROVE, MDC-CC, ULSAM and PIVUS). Intima-media thickness (IMT) was measured by external B-mode ultrasonography at the far wall of the bulb (sinus) and common carotid artery. Plaque presence was defined as a maximal IMT of the bulb >1.5 mm. We meta-analysed single-SNP associations across the four studies, and combined them in a genetic predisposition score. We subsequently examined the association of the genetic predisposition score with prevalent CHD and the three indices of atherosclerosis, adjusting for sex, age and Framingham risk factors.As anticipated, the genetic predisposition score was associated with prevalent CHD, with each additional risk allele increasing the odds of disease by 5.5% (p = 4.1 × 10(-6)). Moreover, each additional CHD-risk allele across the 45 loci was associated with a 0.24% increase in IMT (p = 4.0 × 10(-3)), and with a 2.8% increased odds of plaque presence (p = 7.4 × 10(-6)) at the far wall of the bulb. The genetic predisposition score was not associated with IMT of the common carotid artery (p = 0.47).Our results suggest that the association between the 45 previously identified loci and CHD at least partly acts through atherosclerosis.

SUBMITTER: den Hoed M

PROVIDER: S-EPMC5526440 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

GWAS-identified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb.

den Hoed Marcel M Strawbridge Rona J RJ Almgren Peter P Gustafsson Stefan S Axelsson Tomas T Engström Gunnar G de Faire Ulf U Hedblad Bo B Humphries Steve E SE Lindgren Cecilia M CM Morris Andrew P AP Östling Gerd G Syvänen Ann-Christine AC Tremoli Elena E Hamsten Anders A Ingelsson Erik E Melander Olle O Lind Lars L

Atherosclerosis 20150131 2

<h4>Background</h4>Large-scale genome-wide association studies (GWAS) have so far identified 45 loci that are robustly associated with coronary heart disease (CHD) in data from adult men and women of European descent.<h4>Objectives</h4>To examine whether the CHD-associated loci are associated with measures of atherosclerosis in data from up to 9582 individuals of European ancestry.<h4>Methods</h4>Forty-five SNPs representing the CHD-associated loci were genotyped in middle-aged to elderly indivi ...[more]

PMID: 25682028

Similar Datasets

Project description:BackgroundIntima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.MethodsWe measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.ResultsA total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P=0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P=0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).ConclusionsThe maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.).

Dataset Information

GWAS-identified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb.

Publications

GWAS-identified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets