Dataset Information

Multi-variant study of obesity risk genes in African Americans: The Jackson Heart Study.

ABSTRACT:

Objective

Genome-wide association study (GWAS) has been successful in identifying obesity risk genes by single-variant association analysis. For this study, we designed steps of analysis strategy and aimed to identify multi-variant effects on obesity risk among candidate genes.

Methods

Our analyses were focused on 2137 African American participants with body mass index measured in the Jackson Heart Study and 657 common single nucleotide polymorphisms (SNPs) genotyped at 8 GWAS-identified obesity risk genes.

Results

Single-variant association test showed that no SNPs reached significance after multiple testing adjustment. The following gene-gene interaction analysis, which was focused on SNPs with unadjusted p-value<0.10, identified 6 significant multi-variant associations. Logistic regression showed that SNPs in these associations did not have significant linear interactions; examination of genetic risk score evidenced that 4 multi-variant associations had significant additive effects of risk SNPs; and haplotype association test presented that all multi-variant associations contained one or several combinations of particular alleles or haplotypes, associated with increased obesity risk.

Conclusions

Our study evidenced that obesity risk genes generated multi-variant effects, which can be additive or non-linear interactions, and multi-variant study is an important supplement to existing GWAS for understanding genetic effects of obesity risk genes.

SUBMITTER: Liu S

PROVIDER: S-EPMC5235348 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Multi-variant study of obesity risk genes in African Americans: The Jackson Heart Study.

Liu Shijian S Wilson James G JG Jiang Fan F Griswold Michael M Correa Adolfo A Mei Hao H

Gene 20160826 2

<h4>Objective</h4>Genome-wide association study (GWAS) has been successful in identifying obesity risk genes by single-variant association analysis. For this study, we designed steps of analysis strategy and aimed to identify multi-variant effects on obesity risk among candidate genes.<h4>Methods</h4>Our analyses were focused on 2137 African American participants with body mass index measured in the Jackson Heart Study and 657 common single nucleotide polymorphisms (SNPs) genotyped at 8 GWAS-ide ...[more]

PMID: 27575456

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Project description:ObjectiveReasons for variations in atherosclerotic burden among individuals with similar levels of obesity are poorly understood, especially in African Americans. This study examines whether high-sensitivity C-reactive protein (hsCRP) is useful for discriminating between benign and high-risk obesity phenotypes for subclinical atherosclerosis in African Americans.Approach and resultsParticipants from the Jackson Heart Study (n=4682) were stratified into 4 phenotypes based on the presence of National Heart and Lung and Blood Institute definition of obesity or obesity-equivalent (body mass index ≥30 or body mass index 25-30 with waist circumference >102 cm in men and >88 cm in women) and inflammation by hsCRP ≥2 mg/L. Using multivariate regression models, we conducted cross-sectional analyses of the association between inflammatory obesity phenotypes and subclinical atherosclerosis determined by carotid intima-media thickness or coronary artery calcium scores. Sex-specific analyses were conducted given significant interaction for gender (P=0.03). The prevalence of obesity or equivalent was 65%, of which 30% did not have inflammation. Conversely, 37% of nonobese individuals had inflammation. Among nonobese men, hsCRP ≥2 mg/L identified a subset of individuals with higher carotid intima-media thickness (adjusted mean difference =0.05, 95% confidence interval 0.02, 0.08 mm) compared with their noninflammatory counterparts. Among obese men, hsCRP <2 mg/L identified a subset of individuals with lower coronary artery calcium compared with their inflammatory counterparts. Among women, associations between hsCRP and carotid intima-media thickness or coronary artery calcium were not found.ConclusionsIn the largest African American population-based cohort to date, hsCRP was useful in identifying a subset of nonobese men with higher carotid intima-media thickness, but not in women. hsCRP did not identify a subset of obese individuals with less subclinical atherosclerosis.

Project description:BackgroundRacial differences in rapid kidney function decline exist, but less is known regarding factors associated with rapid decline among African Americans. Greater understanding of potentially modifiable risk factors for early kidney function loss may help reduce the burden of kidney failure in this high-risk population.Study designProspective cohort study.Setting & participants3,653 African American participants enrolled in the Jackson Heart Study (JHS) with kidney function data from 2 of 3 examinations (2000-2004 and 2009-2013). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the CKD-EPI creatinine equation.PredictorsDemographics, socioeconomic status, lifestyle, and clinical risk factors for kidney failure.OutcomesRapid decline was defined as a ≥30% decline in eGFR during follow-up. We quantified the association of risk factors with rapid decline in multivariable models.MeasurementsClinical (systolic blood pressure and albuminuria [albumin-creatinine ratio]) and modifiable risk factors.ResultsMean age was 54±12 (SD) years, 37% were men, average body mass index was 31.8±7.1kg/m(2), 19% had diabetes mellitus (DM), and mean eGFR was 96.0±20mL/min/1.73m(2) with an annual rate of decline of 1.27mL/min/1.73m(2). Those with rapid decline (11.5%) were older, were more likely to be of low/middle income, and had higher systolic blood pressures and greater DM than those with nonrapid decline. Factors associated with ≥30% decline were older age (adjusted OR per 10 years older, 1.51; 95% CI, 1.34-1.71), cardiovascular disease (adjusted OR, 1.53; 95% CI, 1.12-2.10), higher systolic blood pressure (adjusted OR per 17mmHg greater, 1.22; 95% CI, 1.06-1.41), DM (adjusted OR, 2.63; 95% CI, 2.02-3.41), smoking (adjusted OR, 1.60; 95% CI, 1.10-2.31), and albumin-creatinine ratio > 30mg/g (adjusted OR, 1.55; 95% CI, 1.08-1.21). Conversely, results did not support associations of waist circumference, C-reactive protein level, and physical activity with rapid decline.LimitationsNo midstudy creatinine measurement at examination 2 (2005-2008).ConclusionsRapid decline heterogeneity exists among African Americans in JHS. Interventions targeting potentially modifiable factors may help reduce the incidence of kidney failure.

Dataset Information

Multi-variant study of obesity risk genes in African Americans: The Jackson Heart Study.

Objective

Methods

Results

Conclusions

Publications

Multi-variant study of obesity risk genes in African Americans: The Jackson Heart Study.

Similar Datasets

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