Dataset Information

Heritability of Coronary Artery Disease: Insights From a Classical Twin Study.

ABSTRACT:

Background

Genetics have a strong influence on calcified atherosclerotic plaques; however, data regarding the heritability of noncalcified plaque volume are scarce. We aimed to evaluate genetic versus environmental influences on calcium (coronary artery calcification) score, noncalcified and calcified plaque volumes by coronary computed tomography angiography in adult twin pairs without known coronary artery disease.

Methods

In the prospective BUDAPEST-GLOBAL (Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions) classical twin study, we analyzed twin pairs without known coronary artery disease. All twins underwent coronary computed tomography angiography to assess coronary atherosclerotic plaque volumes. Structural equation models were used to quantify the contribution of additive genetic, common environmental, and unique environmental components to plaque volumes adjusted for age, gender, or atherosclerotic cardiovascular disease risk estimate and statin use.

Results

We included 196 twins (mean age±SD, 56±9 years, 63.3% females), 120 monozygotic and 76 same-gender dizygotic pairs. Using structural equation models, noncalcified plaque volume was predominantly determined by environmental factors (common environment, 63% [95% CI, 56%-67%], unique environment, 37% [95% CI, 33%-44%]), while coronary artery calcification score and calcified plaque volumes had a relatively strong genetic heritability (additive genetic, 58% [95% CI, 50%-66%]; unique environmental, 42% [95% CI, 34%-50%] and additive genetic, 78% [95% CI, 73%-80%]; unique environmental, 22% [95% CI, 20%-27%]), respectively.

Conclusions

Noncalcified plaque volume is mainly influenced by shared environmental factors, whereas coronary artery calcification score and calcified plaque volume are more determined by genetics. These findings emphasize the importance of early lifestyle interventions in preventing coronary plaque formation.

Registration

URL: https://www.

Clinicaltrials

gov; Unique identifier: NCT01738828.

SUBMITTER: Drobni ZD

PROVIDER: S-EPMC8925867 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Heritability of Coronary Artery Disease: Insights From a Classical Twin Study.

Drobni Zsofia D ZD Kolossvary Marton M Karady Julia J Jermendy Adam L AL Tarnoki Adam D AD Tarnoki David L DL Simon Judit J Szilveszter Balint B Littvay Levente L Voros Szilard S Jermendy Gyorgy G Merkely Bela B Maurovich-Horvat Pal P

Circulation. Cardiovascular imaging 20220315 3

<h4>Background</h4>Genetics have a strong influence on calcified atherosclerotic plaques; however, data regarding the heritability of noncalcified plaque volume are scarce. We aimed to evaluate genetic versus environmental influences on calcium (coronary artery calcification) score, noncalcified and calcified plaque volumes by coronary computed tomography angiography in adult twin pairs without known coronary artery disease.<h4>Methods</h4>In the prospective BUDAPEST-GLOBAL (Burden of Atheroscle ...[more]

PMID: 35290075

Similar Datasets

Project description:BackgroundGenetic variants currently known to affect coronary artery disease (CAD) risk explain less than one-quarter of disease heritability. The heritability contribution of gene regulatory networks (GRNs) in CAD, which are modulated by both genetic and environmental factors, is unknown.ObjectivesThis study sought to determine the heritability contributions of single nucleotide polymorphisms affecting gene expression (eSNPs) in GRNs causally linked to CAD.MethodsSeven vascular and metabolic tissues collected in 2 independent genetics-of-gene-expression studies of patients with CAD were used to identify eSNPs and to infer coexpression networks. To construct GRNs with causal relations to CAD, the prior information of eSNPs in the coexpression networks was used in a Bayesian algorithm. Narrow-sense CAD heritability conferred by the GRNs was calculated from individual-level genotype data from 9 European genome-wide association studies (GWAS) (13,612 cases, 13,758 control cases).ResultsThe authors identified and replicated 28 independent GRNs active in CAD. The genetic variation in these networks contributed to 10.0% of CAD heritability beyond the 22% attributable to risk loci identified by GWAS. GRNs in the atherosclerotic arterial wall (n = 7) and subcutaneous or visceral abdominal fat (n = 9) were most strongly implicated, jointly explaining 8.2% of CAD heritability. In all, these 28 GRNs (each contributing to >0.2% of CAD heritability) comprised 24 to 841 genes, whereof 1 to 28 genes had strong regulatory effects (key disease drivers) and harbored many relevant functions previously associated with CAD. The gene activity in these 28 GRNs also displayed strong associations with genetic and phenotypic cardiometabolic disease variations both in humans and mice, indicative of their pivotal roles as mediators of gene-environmental interactions in CAD.ConclusionsGRNs capture a major portion of genetic variance and contribute to heritability beyond that of genetic loci currently known to affect CAD risk. These networks provide a framework to identify novel risk genes/pathways and study molecular interactions within and across disease-relevant tissues leading to CAD.

Dataset Information

Heritability of Coronary Artery Disease: Insights From a Classical Twin Study.

Background

Methods

Results

Conclusions

Registration

Clinicaltrials

Publications

Heritability of Coronary Artery Disease: Insights From a Classical Twin Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets