Dataset Information

Association of Exome Sequences With Cardiovascular Traits Among Blacks in the Jackson Heart Study.

ABSTRACT: The correlation of null alleles with human phenotypes can provide insight into gene function in humans. In individuals of African ancestry, we set out to identify null and damaging missense variants, and test these variants for association with a range of cardiovascular phenotypes.We performed whole-exome sequencing in 3223 black individuals from the Jackson Heart Study and found a total of 729?666 variant sites with minor allele frequency <5%, including 17?263 null variants and 49?929 missense variants predicted to be damaging by in silico algorithms. We tested null and damaging missense variants within each gene for association with 36 cardiovascular traits. We found 3 associations that met our prespecified level of significance (?=1.1×10(-7)). Null and damaging missense variants in PCSK9 were associated with 36 mg/dL lower low-density lipoprotein cholesterol (P=3×10(-21)). Three individuals in their 50s with complete PCSK9 deficiency (each compound heterozygote for PCSK9 p.Y142X and p.C679X) were identified, with one having a coronary artery calcification score in the 83rd percentile despite a low-density lipoprotein cholesterol of 32 mg/dL. A damaging missense variant in HBQ1 (p.G52A) was associated with a 2 pg/cell lower mean corpuscular hemoglobin (P=9×10(-13)) and rare damaging missense variants in VPS13A with higher red blood cell distribution width (P=9.9×10(-8)).A limited number of null/damaging alleles with a large effect on cardiovascular traits were detectable in ?3000 black individuals.

SUBMITTER: Peloso GM

PROVIDER: S-EPMC4988917 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Association of Exome Sequences With Cardiovascular Traits Among Blacks in the Jackson Heart Study.

Peloso Gina M GM Lange Leslie A LA Varga Tibor V TV Nickerson Deborah A DA Smith Joshua D JD Griswold Michael E ME Musani Solomon S Polfus Linda M LM Mei Hao H Gabriel Stacey S Quarells Rakale Collins RC Altshuler David D Boerwinkle Eric E Daly Mark J MJ Neale Benjamin B Correa Adolfo A Reiner Alex P AP Wilson James G JG Kathiresan Sekar S

Circulation. Cardiovascular genetics 20160715 4

<h4>Background</h4>The correlation of null alleles with human phenotypes can provide insight into gene function in humans. In individuals of African ancestry, we set out to identify null and damaging missense variants, and test these variants for association with a range of cardiovascular phenotypes.<h4>Methods and results</h4>We performed whole-exome sequencing in 3223 black individuals from the Jackson Heart Study and found a total of 729 666 variant sites with minor allele frequency <5%, incl ...[more]

PMID: 27422940

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Project description:Most studies of depression and cardiovascular risk have been conducted in white populations. We investigated this association in a community-based cohort of blacks.We used data from the Jackson Heart Study to investigate associations of baseline depressive symptoms between 2000 and 2004 with incident stroke and coronary heart disease (CHD) during 10 years. We used Kaplan-Meier estimates and Cox proportional hazards models to assess cardiovascular event risk using 3 exposure variables: any depressive symptoms (Center for Epidemiological Studies Depression score ?16); none (score <16), minor (score 16 to <21), and major depression (score?21); and Center for Epidemiological Studies Depression score per 1-SD increase. Models were adjusted for a stroke or CHD risk score and behavioral risk factors. Of 3309 participants with no stroke history, 738 (22.3%) had baseline depressive symptoms. A similar proportion with no previous CHD had baseline depressive symptoms (21.8%). The unadjusted 10-year risk of stroke was similar among participants with any compared with no depressive symptoms (3.7% versus 2.6%; P=0.12). Unadjusted CHD rates were higher among participants with depressive symptoms (5.6% versus 3.6%; P=0.03), and differences persisted after adjustment for clinical and behavioral risk factors but not after adjustment for coping strategies. In adjusted models comparing major versus no depressive symptoms, patients with major depressive symptoms had a 2-fold greater hazard of stroke (hazard ratio, 1.95; 95% confidence interval, 1.02-3.71; P=0.04). In continuous models, a 1-SD increase in Center for Epidemiological Studies Depression score was associated with a 30% increase in adjusted incident stroke risk (P=0.04). Similar associations were observed for incident CHD in models adjusted for clinical and behavioral risk factors, but associations were not significant after adjustment for coping strategies.In a community-based cohort of blacks, major depressive symptoms were associated with greater risks of incident stroke and CHD after adjustment for clinical and behavioral risk factors.

Project description:BackgroundAmong individuals without hypertension based on clinic blood pressure (BP), it is unclear who should be screened for masked hypertension, defined as having hypertension based on out-of-clinic BP. We hypothesized that individuals with a higher 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk, calculated using the pooled cohort risk equations, have a higher prevalence of masked hypertension.Methods and resultsWe analyzed data from the Jackson Heart Study-a population-based cohort of blacks-to determine the association of predicted ASCVD risk with masked hypertension. The sample included 644 participants, 40 to 79 years of age, with clinic systolic/diastolic BP <140/90 mm Hg, who completed ambulatory BP monitoring, were free of cardiovascular disease, and had data on factors needed to calculate ASCVD risk. Ten-year predicted ASCVD risk was calculated using the pooled cohort risk equations. Any masked hypertension was defined as masked daytime hypertension (mean daytime systolic/diastolic BP ≥135/85 mm Hg), masked nighttime hypertension (mean nighttime systolic/diastolic BP ≥120/70 mm Hg), or masked 24-hour hypertension (mean 24-hour systolic/diastolic BP ≥130/80 mm Hg). The prevalence of any masked hypertension was 54.0%. Compared with participants in the lowest (<5%) predicted ASCVD risk category, multivariable-adjusted prevalence ratios (95% confidence interval) for any masked hypertension were 1.36 (1.03-1.79), 1.62 (1.22-2.16), and 1.91 (1.47-2.48) for those with ASCVD risk of 5% to <7.5%, 7.5% to <10%, and ≥10%, respectively. The C statistic for discriminating between participants with versus without any masked hypertension was 0.681 (95% confidence interval, 0.640-0.723) for ASCVD risk and 0.703 (95% confidence interval, 0.663-0.744) for clinic systolic BP and diastolic BP.ConclusionsHigher ASCVD risk was associated with an increased prevalence of masked hypertension. Although the discrimination of ASCVD risk for masked hypertension was not superior to clinic BP, risk prediction equations may be useful for identifying the subgroup of individuals with both masked hypertension and high predicted ASCVD risk.

Dataset Information

Association of Exome Sequences With Cardiovascular Traits Among Blacks in the Jackson Heart Study.

Publications

Association of Exome Sequences With Cardiovascular Traits Among Blacks in the Jackson Heart Study.

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