Epigenetic markers of renal function in african americans.
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ABSTRACT:
SUBMITTER: Bomotti SM
PROVIDER: S-EPMC3874945 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR). We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans.
| S-EPMC3441677 | biostudies-literature
Project description:Obesity prevalence in United States (US) adults exceeds 30% with highest prevalence being among blacks. Obesity is known to have significant effects on respiratory function and obese patients commonly report respiratory complaints requiring pulmonary function tests (PFTs). However, there is no large study showing the relationship between body mass index (BMI) and PFTs in healthy African Americans (AA).To determine the effect of BMI on PFTs in AA patients who did not have evidence of underlying diseases of the respiratory system.We reviewed PFTs of 339 individuals sent for lung function testing who had normal spirometry and lung diffusion capacity for carbon monoxide (DLCO) with wide range of BMI.Functional residual capacity (FRC) and expiratory reserve volume (ERV) decreased exponentially with increasing BMI, such that morbid obesity resulted in patients breathing near their residual volume (RV). However, the effects on the extremes of lung volumes, at total lung capacity (TLC) and residual volume (RV) were modest. There was a significant linear inverse relationship between BMI and DLCO, but the group means values remained within the normal ranges even for morbidly obese patients.We showed that BMI has significant effects on lung function in AA adults and the greatest effects were on FRC and ERV, which occurred at BMI values < 30 kg/m2. These physiological effects of weight gain should be considered when interpreting PFTs and their effects on respiratory symptoms even in the absence of disease and may also exaggerate existing lung diseases.
| S-EPMC4619259 | biostudies-literature
Project description:ObjectivesTo examine associations between specific inflammatory biomarkers and cognitive function in African Americans (AAs) and European Americans (EAs) with prevalent vascular risk factors.DesignCross-sectional analysis using generalized estimating equations to account for familial clustering; standardized β-coefficients, adjusted for age, sex, and education are reported.SettingCommunity cohort study in Jackson, Mississippi, and Rochester, Minnesota.ParticipantsGenetic Epidemiology Network of Arteriopathy (GENOA)-Genetics of Microangiopathic Brain Injury (GMBI) Study participants.MeasurementsAssociations between inflammation (high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, soluble tumor necrosis factor (TNF) receptor 1 and 2 (sTNFR1, sTNFR2)) and cognitive function (global, processing speed, language, memory, and executive function) were examined in AAs and EAs (N = 1,965; aged 26-95, 64% women, 52% AA, 75% with hypertension).ResultsIn AAs, higher sTNFR2 was associated with poorer cognition in all domains (global: -0.11, P = .009; processing speed: -0.11, P < .001; language: -0.08, P = .002; memory: -0.09, P = .008; executive function: -0.07, P = .03); sTNFR1 was associated with slower processing speed (-0.08, P < .001) and poorer executive function (-0.08, P = .008); higher CRP was associated with slower processing speed (-0.04, P = .024), and higher IL6 was associated with poorer executive function (-0.07, P = .02). In EA, only higher sTNFR1 was associated with slower processing speed (-0.05, P = .007). Associations were not found between cognition and sTNFR2, CRP, or IL6 in EA.ConclusionIn a population with high vascular risk, adverse associations between inflammation and cognitive function were especially apparent in AAs, primarily involving markers of TNFα activity.
| S-EPMC4270090 | biostudies-literature
Project description:Adverse housing and neighborhood conditions are independently associated with an increased risk of various diseases and conditions. One possible explanation relates to systemic inflammation, which is associated with these adverse health outcomes. The authors investigated the association between housing and neighborhood conditions with inflammatory markers using data about 352 persons aged 49-65 years from the African American Health study. Participants were identified by a multistage random selection process in 2000 to 2001(response rate, 76%). Blood was analyzed for soluble cytokine receptors (interleukin-6, tumor necrosis factor alpha), C-reactive protein, and adiponectin. Neighborhood and housing characteristics consisted of five observed block face conditions (external appearance of the block on which the subject lived), four perceived neighborhood conditions, four observed housing conditions (home assessment by the interviewers rating the interior and exterior of the subject's building), and census-tract level poverty rate from the 2000 census. Differences in some inflammatory markers were found by age, gender, chronic conditions, and body mass index (all Bonferroni-adjusted p < 0.0034). There was no association between any of the housing/neighborhood conditions and the pro-inflammatory markers and potential associations between some housing/neighborhood conditions and adiponectin (p < 0.05, Bonferroni-adjusted p > 0.0034). Inflammation does not appear to be a mediator of the association between poor housing/neighborhood conditions and adverse health outcomes in middle-aged African Americans.
| S-EPMC2845834 | biostudies-other
Project description:Renal dysfunction is prevalent in the US among African Americans. Air pollution is associated with renal dysfunction in mostly white American populations, but has not been studied among African Americans. We evaluated cross-sectional associations between 1-year and 3-year fine particulate matter (PM2.5) and ozone (O3) concentrations, and renal function among 5090 African American participants in the Jackson Heart Study. We used mixed-effect linear regression to estimate associations between 1-year and 3-year PM2.5 and O3 and estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio (UACR), serum creatinine, and serum cystatin C, adjusting for: sociodemographic factors, health behaviors, and medical history and accounting for clustering by census tract. At baseline, JHS participants had mean age 55.4 years, and 63.8% were female; mean 1-year and 3-year PM2.5 concentrations were 12.2 and 12.4 µg/m3, and mean 1-year and 3-year O3 concentrations were 40.2 and 40.7 ppb, respectively. Approximately 6.5% of participants had reduced eGFR (< 60 mL/min/1.73m2) and 12.7% had elevated UACR (> 30 mg/g), both indicating impaired renal function. Annual and 3-year O3 concentrations were inversely associated with eGFR and positively associated with serum creatinine; annual and 3-year PM2.5 concentrations were inversely associated with UACR. We observed impaired renal function associated with increased O3 but not PM2.5 exposure among African Americans.
| S-EPMC6511484 | biostudies-literature
Project description:Genetic admixture has been utilized as a tool for identifying loci associated with complex traits and diseases in recently admixed populations such as African Americans. In particular, admixture mapping is an efficient approach to identifying genetic basis for those complex diseases with substantial racial or ethnic disparities. Though current advances in admixture mapping algorithms may utilize the entire panel of SNPs, providing ancestry-informative markers (AIMs) that can differentiate parental populations and estimate ancestry proportions in an admixed population may particularly benefit admixture mapping in studies of limited samples, help identify unsuitable individuals (e.g., through genotyping the most informative ancestry markers) before starting large genome-wide association studies (GWAS), or guide larger scale targeted deep re-sequencing for determining specific disease-causing variants. Defining panels of AIMs based on commercial, high-throughput genotyping platforms will facilitate the utilization of these platforms for simultaneous admixture mapping of complex traits and diseases, in addition to conventional GWAS. Here, we describe AIMs detected based on the Shannon Information Content (SIC) or Fst for African Americans with genome-wide coverage that were selected from ∼2.3 million single nucleotide polymorphisms (SNPs) covered by the Affymetrix Axiom Pan-African array, a newly developed genotyping platform optimized for individuals of African ancestry.
| S-EPMC4226639 | biostudies-literature
Project description:This study examined multiple influences on cognitive function among African Americans, including education, literacy, poverty status, substance use, depressive symptoms, and cardiovascular disease (CVD) risk factors. Baseline data were analyzed from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Participants were 987 African Americans (mean age 48.5 years, SD = 9.17) who completed cognitive measures assessing verbal learning and memory, nonverbal memory, working memory, verbal fluency, perceptuo-motor speed, attention, and cognitive flexibility. Using preplanned hierarchical regression, cognitive performance was regressed on the following: (1) age, sex, education, poverty status; (2) literacy; (3) cigarette smoking, illicit substance use; (4) depressive symptoms; and (5) number of CVD risk factors. Results indicated that literacy eliminated the influence of education and poverty status in select instances, but added predictive utility in others. In fully adjusted models, results showed that literacy was the most important influence on cognitive performance across all cognitive domains (p < .001); however, education and poverty status were related to attention and cognitive flexibility. Depressive symptoms and substance use were significant predictors of multiple cognitive outcomes, and CVD risk factors were not associated with cognitive performance. Overall, findings underscore the need to develop cognitive supports for individuals with low literacy, educational attainment, and income, and the importance of treating depressive symptoms and thoroughly examining the role of substance use in this population.
| S-EPMC7418872 | biostudies-literature
Project description:As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.
| S-EPMC2614692 | biostudies-literature
Project description:Genome-wide association studies (GWAS) of renal cell carcinoma (RCC) in populations of European ancestry have identified four susceptibility loci. No GWAS has been conducted among African Americans (AA), who experience a higher incidence of RCC. We conducted a GWAS in which we analyzed 1,136,723 common single-nucleotide polymorphisms (SNP) among 255 cases and 375 controls of African ancestry, and further investigated 16 SNPs in a replication set (140 cases and 543 controls). The 12p11.23 variant rs10771279, located 77 kb from the European-ancestry RCC marker rs718314, was associated with RCC risk in the GWAS (P = 1.2 × 10(-7)) but did not replicate (P = 0.99). Consistent with European-ancestry findings, the A allele of rs7105934 on 11q13.3 was associated with decreased risk [OR, 0.76, 95% confidence interval (CI), 0.64-0.91; P = 0.0022]. The frequency of this allele was higher than that observed in the European-ancestry GWAS (0.56 and 0.07, respectively, among controls). The rs7105934 association was stronger for clear cell RCC (ccRCC: OR, 0.56; P = 7.4 × 10(-7)) and absent for cases of other or unknown histology (OR, 1.02; P = 0.86). Analyses of rs7105934 by subtype among European-ancestry participants from these studies yielded similar findings (ORs 0.69 and 0.92, respectively). This study provides, to our knowledge, the first evidence that rs7105934 is an RCC susceptibility locus among AAs. Our finding that the association with this SNP may be specific to clear-cell RCC is novel and requires additional investigation. Additional investigation of rs10771279 and other suggestive GWAS findings is also needed.
| S-EPMC3901793 | biostudies-literature
Project description:The vascular ectonucleotidase ENTPD1 protects against renal injury and modulates glucose homeostasis in mouse models. We sought to determine whether human variation in ENTPD1 influences predisposition to diabetes or diabetic nephropathy.We analyzed ENTPD1 single nucleotide polymorphisms (SNPs) in 363 African American control subjects, 380 subjects with type 2 diabetes and end-stage renal disease (DM-ESRD), and 326 subjects with ESRD unrelated to diabetes (non-DM-ESRD). Using human cell lines, we correlated disease-associated ENTPD1 haplotypes with ENTPD1 gene expression. Finally, we studied consequences of ENTPD1 deletion in a mouse model of type 2 diabetes (db/db).A common ENTPD1 two-SNP haplotype was associated with increased risk for DM-ESRD (P = 0.0027), and an uncommon four-SNP haplotype was associated with protection against DM-ESRD (P = 0.004). These haplotypes correlated with ENTPD1 gene expression levels in human cell lines in vitro. Subjects with high ENTPD1-expressing haplotypes were enriched in the DM-ESRD group. By crossing ENTPD1-null mice with db mice, we show that ENTPD1 deletion has prominent effects on metabolic syndrome traits. Specifically, deletion of ENTPD1 lowered glucose levels in control (db/-) mice with one functional leptin receptor and dramatically lowered weights in db/db mice with no functional leptin receptors. Similar effects were seen in aged ENTPD1-null mice with normal leptin receptors.ENTPD1 polymorphisms appear to influence susceptibility to type 2 diabetes and/or diabetic nephropathy in African Americans. Studies in human cell lines and in vivo mouse data support a potential role for ENTPD1 genetic variation in susceptibility to type 2 diabetes.
| S-EPMC2661602 | biostudies-literature