Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes

Abstract

BackgroundCoronary artery calcified atherosclerotic plaque (CAC) predicts cardiovascular disease (CVD). Despite exposure to more severe conventional CVD risk factors, African Americans (AAs) are less likely to develop CAC, and when they do, have markedly lower levels than European Americans. Genetic factors likely contribute to the observed ethnic differences. To identify genes associated with CAC in AAs with type 2 diabetes (T2D), a genome-wide association study (GWAS) was performed using the Illumina 5 M chip in 691 African American-Diabetes Heart Study participants (AA-DHS), with replication in 205 Jackson Heart Study (JHS) participants with T2D. Genetic association tests were performed on the genotyped and 1000 Genomes-imputed markers separately for each study, and combined in a meta-analysis.ResultsSingle nucleotide polymorphisms (SNPs), rs11353135 (2q22.1), rs16879003 (6p22.3), rs5014012, rs58071836 and rs10244825 (all on chromosome 7), rs10918777 (9q31.2), rs13331874 (16p13.3) and rs4459623 (18q12.1) were associated with presence and/or quantity of CAC in the AA-DHS and JHS, with meta-analysis p-values ≤8.0 × 10−7. The strongest result in AA-DHS alone was rs6491315 in the 13q32.1 region (parameter estimate (SE) = −1.14 (0.20); p-value = 9.1 × 10−9). This GWAS peak replicated a previously reported AA-DHS CAC admixture signal (rs7492028, LOD score 2.8).ConclusionsGenetic association between SNPs on chromosomes 2, 6, 7, 9, 16 and 18 and CAC were detected in AAs with T2D from AA-DHS and replicated in the JHS. These data support a role for genetic variation on these chromosomes as contributors to CAC in AAs with T2D, as well as to variation in CAC between populations of African and European ancestry.Electronic supplementary materialThe online version of this article (10.1186/s12863-017-0572-9) contains supplementary material, which is available to authorized users.

DNA Methylation Biomarkers Of Myocardial Infarction And Cardiovascular Disease

“…These findings are consistent with previous studies [9,36,38,52–54]. Genetic variants in CPTA1 have also been associated with calcified atherosclerotic plaque in coronary artery [55].…”

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

“…In several genome-wide association studies, genetic risk factors for arterial calcification have been descibed such as TCF7L2 and WWOX (in smoker) and TNFRSF8 (in non-smoker) in patients with coronary artery calcification (CAC) [6]; 9p21-rs4977574, ADAMTS7-rs3825807, and PHACTR1-rs12526453 in patients with coronary artery disease (CAD) and myocardial infarction (MI) [7], CDKN2A, CDKN2B-rs1333049, rs9349379-PHACTR1, MRAS, COL4A1/COL4A2, and SORT1 genes in MI [8]; 9p2-1rs16905644 and PHACTR1 in patients with CAC [9]; rs11353135-2q22.1, rs16879003-6p22.3, rs5014012, rs58071836, rs10244825 on chromosome 7, 9q31.2-rs10918777, 16p13.3-rs13331874, 18q12.1-rs4459623, 13q32.1-rs6491315, and 13q32-rs7492028 in patients with type 2 diabetes [10]. Interestingly, based on these studies, there is an overlap of risk genetic loci between arterial calcification and MI, indicating shared pathological components.…”

Cardiac imaging of aortic valve area from 26,142 UK Biobank participants reveal novel genetic associations and shared genetic comorbidity with multiple disease phenotypes

“…The identified region on chromosome 12 displays an intronic variant in the CRADD gene as a top marker. Variation mapping to CRADD has been previously related to coronary artery calcification 27 , a phenotype strongly linked to calcific aortic valve disease and aortic stenosis 28 . The PheWAS data for rs71190365 indicate a link to known cardiac comorbidities such as forced expiratory volume and body mass, which may represent a pleiotropic effect-decreased area of the aortic valve is a determinant of cardiac output which governs cardiac output and exercise capacity 29 .…”