Race-specific alterations in DNA methylation among middle-aged African Americans and Whites with metabolic syndrome.
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ABSTRACT:
SUBMITTER: Chitrala KN
PROVIDER: S-EPMC7188395 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAfrican Americans (AAs) experience premature chronic health outcomes and longevity disparities consistent with an accelerated aging phenotype. DNA methylation (DNAm) levels at specific CpG positions are hallmarks of aging evidenced by the presence of age-associated differentially methylated CpG positions (aDMPs) that are the basis for the epigenetic clock for measuring biological age acceleration. Since DNAm has not been widely studied among non-European populations, we examined the association between DNAm and chronological age in AAs and whites, and the association between race, poverty, sex, and epigenetic age acceleration.ResultsWe measured genome-wide DNA methylation (866,836 CpGs) using the Illumina MethylationEPIC BeadChip in blood DNA extracted from 487 middle-aged AA (N = 244) and white (N = 243), men (N = 248), and women (N = 239). The mean (sd) age was 48.4 (8.8) in AA and 49.0 (8.7) in whites (p = 0.48). We identified 4930 significantly associated aDMPs in AAs and 469 in whites. Of these, 75.6% and 53.1% were novel, largely driven by the increased number of measured CpGs in the EPIC array, in AA and whites, respectively. AAs had more age-associated DNAm changes than whites in genes implicated in age-related diseases and cellular pathways involved in growth and development. We assessed three epigenetic age acceleration measures (universal, intrinsic, and extrinsic). AAs had a significantly slower extrinsic aging compared to whites. Furthermore, compared to AA women, both AA and white men had faster aging in the universal age acceleration measure (+ 2.04 and + 1.24 years, respectively, p < 0.05).ConclusionsAAs have more wide-spread methylation changes than whites. Race and sex interact to underlie biological age acceleration suggesting altered DNA methylation patterns may be important in age-associated health disparities.
| S-EPMC6700815 | biostudies-literature
Project description:Diabetes predicts late-life dementia, but the association with rate of cognitive decline is inconsistent and has rarely been examined in non-white populations, despite the high prevalence of diabetes in African Americans. We evaluated the effect of diabetes on cognitive decline in middle-aged African Americans and whites.Atherosclerosis Risk in Communities (ARIC) Brain MRI Study participants (n = 1,886, mean age = 60, 49% African American) underwent assessments of verbal memory, processing speed, and verbal fluency four times over 14 years. Using race-stratified mixed linear effects models, we examined cognitive change for participants with prevalent (baseline) diabetes and incident (diagnosed after baseline) diabetes versus those without diabetes.African Americans had more advanced diabetes, as indicated by fasting blood glucose levels, anti-diabetes medication use, and cardiovascular risk profiles. African Americans with prevalent diabetes experienced 41% greater annual decline in processing speed scores (p = 0.048) and 50% greater annual decline in verbal fluency scores (p = 0.042) than those without diabetes; incident diabetes was not associated with cognitive decline. Among whites, diabetes was not associated with cognitive decline.Prevalent diabetes was associated with greater cognitive decline in middle-aged African Americans, possibly reflecting adverse effects of longer duration and more advanced diabetes.
| S-EPMC4370220 | 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:BackgroundObesity and multimorbidity are more prevalent among U.S. racial/ethnic minority groups. Evaluating racial/ethnic disparities in disease accumulation according to body mass index (BMI) may guide interventions to reduce multimorbidity burden in vulnerable racial/ethnic groups.MethodWe used data from the 1998-2016 Health and Retirement Study on 8 106 participants aged 51-55 at baseline. Disease burden and multimorbidity (≥2 co-occurring diseases) were assessed using 7 chronic diseases: arthritis, cancer, heart disease, diabetes, hypertension, lung disease, and stroke. Four BMI categories were defined per convention: normal, overweight, obese class 1, and obese class 2/3. Generalized estimating equations models with inverse probability weights estimated the accumulation of chronic diseases.ResultsOverweight and obesity were more prevalent in non-Hispanic Black (82.3%) and Hispanic (78.9%) than non-Hispanic White (70.9 %) participants at baseline. The baseline burden of disease was similar across BMI categories, but disease accumulation was faster in the obese class 2/3 and marginally in the obese class 1 categories compared with normal BMI. Black participants across BMI categories had a higher initial burden and faster accumulation of disease over time, while Hispanics had a lower initial burden and similar rate of accumulation, compared with Whites. Black participants, including those with normal BMI, reach the multimorbidity threshold 5-6 years earlier compared with White participants.ConclusionsControlling weight and reducing obesity early in the lifecourse may slow the progression of multimorbidity in later life. Further investigations are needed to identify the factors responsible for the early and progressing nature of multimorbidity in Blacks of nonobese weight.
| S-EPMC8824553 | biostudies-literature
Project description:With the rapid advancement of omics-based research, particularly big data such as genome- and epigenome-wide association studies that include extensive environmental and clinical variables, data analytics have become increasingly complex. Researchers face significant challenges regarding how to analyze multifactorial data and make use of the findings for clinical translation. The purpose of this article is to provide a scientific exemplar for use of genetic burden scores as a data analysis method for studies with both genotype and DNA methylation data in which the goal is to evaluate associations with chronic conditions such as metabolic syndrome (MetS). This study included 739 African American men and women from the Genetic Epidemiology Network of Arteriopathy Study who met diagnostic criteria for MetS and had available genetic and epigenetic data. Genetic burden scores for evaluated genes were not significant after multiple testing corrections, but DNA methylation at 2 CpG sites (dihydroorotate dehydrogenase cg22381196 pFDR = .014; CTNNA3 cg00132141 pFDR = .043) was significantly associated with MetS after controlling for multiple comparisons. Interactions between the marginally significant CpG sites and burden scores, however, were not significant. More work is required in this area to identify intermediate biological pathways influenced by environmental, genetic, and epigenetic variation that may explain the high prevalence of MetS among African Americans. This study does serve, however, as an example of the use of the genetic burden score as an alternative data analysis approach for complex studies involving the analysis of genetic and epigenetic data simultaneously.
| S-EPMC6700897 | biostudies-literature
Project description:Cadmium (Cd) is a ubiquitous environmental pollutant associated with a wide range of health outcomes including cancer. However, obscure exposure sources often hinder prevention efforts. Further, although epigenetic mechanisms are suspected to link these associations, gene sequence regions targeted by Cd are unclear. Aberrant methylation of a differentially methylated region (DMR) on the MEG3 gene that regulates the expression of a cluster of genes including MEG3, DLK1, MEG8, MEG9 and DIO3 has been associated with multiple cancers. In 287 infant-mother pairs, we used a combination of linear regression and the Getis-Ord Gi* statistic to determine if maternal blood Cd concentrations were associated with offspring CpG methylation of the sequence region regulating a cluster of imprinted genes including MEG3. Correlations were used to examine potential sources and routes. We observed a significant geographic co-clustering of elevated prenatal Cd levels and MEG3 DMR hypermethylation in cord blood (P = 0.01), and these findings were substantiated in our statistical models (β = 1.70, se = 0.80, P = 0.03). These associations were strongest in those born to African American women (β = 3.52, se = 1.32, P = 0.01) compared with those born to White women (β = 1.24, se = 2.11, P = 0.56) or Hispanic women (β = 1.18, se = 1.24, P = 0.34). Consistent with Cd bioaccumulation during the life course, blood Cd levels increased with age (β = 0.015 µg/dl/year, P = 0.003), and Cd concentrations were significantly correlated between blood and urine (ρ > 0.47, P < 0.01), but not hand wipe, soil or house dust concentrations (P > 0.05). Together, these data support that prenatal Cd exposure is associated with aberrant methylation of the imprint regulatory element for the MEG3 gene cluster at birth. However, neither house-dust nor water are likely exposure sources, and ingestion via contaminated hands is also unlikely to be a significant exposure route in this population. Larger studies are required to identify routes and sources of exposure.
| S-EPMC6736358 | biostudies-literature
Project description:The BTNL2 gene is a member of the B7 receptor family that probably functions as a T-cell costimulatory molecule. It resides in the class II major histocompatibility complex (MHC) region of chromosome 6p and has recently been associated with sarcoidosis susceptibility in a white German population. We sought to replicate the BTNL2 association in an African American family-based study population (n=219 nuclear families) and two case-control populations--one African American (n=295 pairs) and one white (n=366 pairs). Ten SNPs were detected within a 490-bp region spanning exon/intron 5 of BTNL2. Haplotype variation within this region was significantly associated with sarcoidosis in all three study populations but more so in whites (P=.0006) than in the African American case-control (P=.02) or family-based (P=.03) samples. The previously reported BTNL2 SNP with the strongest sarcoidosis association, rs2076530, was also the SNP with the strongest association in our white population (P<.0001). The A allele of rs2076530 results in a premature exon-splice site and increases risk for sarcoidosis (odds ratio=2.03; 95% confidence interval 1.32-3.12). Although rs2076530 was not associated with sarcoidosis in either African American sample, a three-locus haplotype that included rs2076530 was associated with sarcoidosis across all three study samples. Multivariable logistic regression analyses showed that BTNL2 effects are independent of human leukocyte antigen class II genes in whites but may interact antagonistically in African Americans. Our results underscore the complexity of genetic risk for sarcoidosis emanating from the MHC region.
| S-EPMC1226214 | biostudies-literature
Project description:IntroductionUrban environments are associated with a higher risk of adverse mental health outcomes; however, it is unclear which specific components of the urban environment drive these associations.MethodsUsing data collected in 2002-2009 from 73,225 low-income, racially diverse individuals across the Southeastern U.S., analyses evaluated the cross-sectional relationship between a walkability index and depression. Walkability was calculated from population density, street connectivity, and destination count in the 1,200-meter area around participants' homes, and depression was measured using the Center for Epidemiologic Studies Depression Scale for depression symptomatology and questionnaire responses regarding doctor-diagnosed depression and antidepressant use. Data were analyzed in 2015.ResultsParticipants living in neighborhoods with the highest walkability index had 6% higher odds of moderate or greater depression symptoms (score ≥15, 95% CI=0.99, 1.14), 28% higher odds of doctor-diagnosed depression (95% CI=1.20, 1.36), and 16% higher odds of current antidepressant use (95% CI=1.08, 1.25), compared with those in the lowest walkability index. Higher walkability was associated with higher odds of depression symptoms in the most deprived neighborhoods only, whereas walkability was associated with lower odds of depression symptoms in the least deprived neighborhoods.ConclusionsLiving in a more walkable neighborhood was associated with modestly higher levels of doctor-diagnosed depression and antidepressant use, and walkability was associated with greater depression symptoms in neighborhoods with higher deprivation. Although dense urban environments may provide opportunities for physical activity, they may also increase exposure to noise, air pollution, and social stressors that could increase levels of depression.
| S-EPMC5167658 | biostudies-literature
Project description:BACKGROUND:We sought to validate a recently published risk algorithm for incident atrial fibrillation (AF) in independent cohorts and other racial groups. METHODS:We evaluated the performance of a Framingham Heart Study (FHS)-derived risk algorithm modified for 5-year incidence of AF in the FHS (n = 4764 participants) and 2 geographically and racially diverse cohorts in the age range 45 to 95 years: AGES (the Age, Gene/Environment Susceptibility-Reykjavik Study) (n = 4238) and CHS (the Cardiovascular Health Study) (n = 5410, of whom 874 [16.2%] were African Americans). The risk algorithm included age, sex, body mass index, systolic blood pressure, electrocardiographic PR interval, hypertension treatment, and heart failure. RESULTS:We found 1359 incident AF events in 100 074 person-years of follow-up. Unadjusted 5-year event rates differed by cohort (AGES, 12.8 cases/1000 person-years; CHS whites, 22.7 cases/1000 person-years; and FHS, 4.5 cases/1000 person-years) and by race (CHS African Americans, 18.4 cases/1000 person-years). The strongest risk factors in all samples were age and heart failure. The relative risks for incident AF associated with risk factors were comparable across cohorts and race groups. After recalibration for baseline incidence and risk factor distribution, the Framingham algorithm, reported in C statistic, performed reasonably well in all samples: AGES, 0.67 (95% confidence interval [CI], 0.64-0.71); CHS whites, 0.68 (95% CI, 0.66-0.70); and CHS African Americans, 0.66 (95% CI, 0.61-0.71). Risk factors combined in the algorithm explained between 47.0% (AGES) and 63.6% (FHS) of the population-attributable risk. CONCLUSIONS:Risk of incident AF in community-dwelling whites and African Americans can be assessed reliably by routinely available and potentially modifiable clinical variables. Seven risk factors accounted for up to 64% of risk.
| S-EPMC3021784 | biostudies-literature
Project description:Pulse pressure (an indirect measure of arterial stiffness) is a robust predictor of cardiovascular events, but its pathophysiology remains poorly understood. To gain insight into the pathophysiology of arterial stiffness we conducted an exploratory investigation of the associations of 47 circulating biomarkers in etiologic pathways of arteriosclerosis with brachial artery pulse pressure.Participants included 1,193 African-Americans and 1,145 non-Hispanic whites belonging to hypertensive sibships. Blood pressure (BP) was measured with a random-zero sphygmomanometer. Multivariable linear regression was employed to assess the associations of biomarkers with pulse pressure after adjustment for age, sex, conventional risk factors, mean arterial pressure, heart rate, and use of aspirin, statins, estrogens, and antihypertensives. Statistical significance was set at P ? 0.001 (Bonferroni correction for multiple testing).Log N-terminal probrain natriuretic peptide (NT-proBNP) (African-Americans: ? = 2.11 ± 0.52, non-Hispanic whites: ? = 2.65 ± 0.55), log midregional proatrial natriuretic peptide (African-Americans: ? = 4.83 ± 0.70, non-Hispanic whites: ? = 3.70 ± 0.67), and log osteoprotegerin (African-Americans: ? = 4.64 ± 1.02, non-Hispanic whites: ? = 4.19 ± 0.99) were independently associated with pulse pressure (P < 0.001 for all) in both ethnicities. Log C-reactive protein (CRP) (? = 1.56 ± 0.35), log midregional proadrenomedullin (MR-proADM) (? = 5.53 ± 1.19) and log matrix metalloproteinase-2 (? = 3.89 ± 1.06) were associated with greater pulse pressure in African-Americans only (P ? 0.001 for all), whereas higher fibrinogen was associated with pulse pressure in non-Hispanic whites only (? = 0.02 ± 0.004. P < 0.001).Our results suggest that hemodynamic stress, vascular inflammation and calcification, and matrix remodeling may have a role in the pathogenesis and/or adverse consequences of increased pulse pressure.
| S-EPMC3707798 | biostudies-literature