Dataset Information

Analysis of common and coding variants with cardiovascular disease in the Diabetes Heart Study.

ABSTRACT: Type 2 diabetes mellitus (T2DM) is a major cardiovascular disease (CVD) risk factor. Identification of genetic risk factors for CVD is important to understand disease risk. Two recent genome-wide association study (GWAS) meta-analyses in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium detected CVD-associated loci.Variants identified in CHARGE were tested for association with CVD phenotypes, including vascular calcification, and conventional CVD risk factors, in the Diabetes Heart Study (DHS) (n?=?1208; >80% T2DM affected). This included 36 genotyped or imputed single nucleotide polymorphisms (SNPs) from DHS GWAS data. 28 coding SNPs from 14 top CHARGE genes were also identified from exome sequencing resources and genotyped, along with 209 coding variants from the Illumina HumanExome BeadChip genotype data in the DHS were also tested. Genetic risk scores (GRS) were calculated to evaluate the association of combinations of variants with CVD measures.After correction for multiple comparisons, none of the CHARGE SNPs were associated with vascular calcification (p?

SUBMITTER: Adams JN

PROVIDER: S-EPMC4021556 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Analysis of common and coding variants with cardiovascular disease in the Diabetes Heart Study.

Adams Jeremy N JN Raffield Laura M LM Freedman Barry I BI Langefeld Carl D CD Ng Maggie C Y MC Carr J Jeffrey JJ Cox Amanda J AJ Bowden Donald W DW

Cardiovascular diabetology 20140412

<h4>Background</h4>Type 2 diabetes mellitus (T2DM) is a major cardiovascular disease (CVD) risk factor. Identification of genetic risk factors for CVD is important to understand disease risk. Two recent genome-wide association study (GWAS) meta-analyses in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium detected CVD-associated loci.<h4>Methods</h4>Variants identified in CHARGE were tested for association with CVD phenotypes, including vascular calcification, ...[more]

PMID: 24725463

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Project description:Background and objectivesBlacks have high rates of cardiovascular disease and mortality. Diabetes and CKD, risk factors for cardiovascular mortality in the general population, are common among blacks. We sought to assess their contribution to cardiovascular disease and mortality in blacks.Design, setting, participants, & measurementsThis observational cohort study was of 3211 participants in the Jackson Heart Study (enrolled 2000-2004). Rates of incident stroke, incident coronary heart disease, and cardiovascular mortality were quantified in participants with diabetes, CKD (eGFR<60 ml/min per 1.73 m(2), urine albumin-to-creatinine ratio ≥30 mg/g, or both), or both through 2012, with a median follow-up of 6.99 years.ResultsFour hundred fifty-six (14.2%) participants had only diabetes, 257 (8.0%) had only CKD, 201 (6.3%) had both, and 2297 (71.5%) had neither. Diabetes without CKD was associated with excess risks of incident stroke, incident coronary heart disease, and cardiovascular mortality after adjustment for demographic and clinical covariates, including prevalent cardiovascular disease (excess incidence rates, 2.6; 95% confidence interval, 0.5 to 4.7; 2.6; 95% confidence interval, 0.3 to 4.8; and 2.4; 95% confidence interval, 0.4 to 4.3 per 1000 person-years, respectively). CKD without diabetes was associated with comparable nonsignificant excess risks for incident stroke and coronary heart disease (2.5; 95% confidence interval, -0.1 to 5.2 and 2.4; 95% confidence interval, -0.8 to 5.5 per 1000 person-years, respectively) but a larger excess risk for cardiovascular mortality (7.3; 95% confidence interval, 3.0 to 11.5 per 1000 person-years). Diabetes and CKD together were associated with greater excess risks for incident stroke (13.8; 95% confidence interval, 5.3 to 22.3 per 1000 person-years), coronary heart disease (12.8; 95% confidence interval, 4.9 to 20.8 per 1000 person-years), and cardiovascular mortality (14.8; 95% confidence interval, 7.2 to 22.3 per 1000 person-years). The excess risks associated with the combination of diabetes and CKD were larger than those associated with established risk factors, including prevalent cardiovascular disease.ConclusionsThe combination of diabetes and kidney disease is associated with substantial excess risks of cardiovascular events and mortality among blacks.

Dataset Information

Analysis of common and coding variants with cardiovascular disease in the Diabetes Heart Study.

Publications

Analysis of common and coding variants with cardiovascular disease in the Diabetes Heart Study.

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