A PheWAS study of a large observational epidemiological cohort of African Americans from the REGARDS study.
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SUBMITTER: Zhao X
PROVIDER: S-EPMC6357353 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
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A PheWAS study of a large observational epidemiological cohort of African Americans from the REGARDS study.
Zhao Xueyan X Geng Xin X Srinivasasainagendra Vinodh V Chaudhary Ninad N Judd Suzanne S Wadley Virginia V Gutiérrez Orlando M OM Wang Henry H Lange Ethan M EM Lange Leslie A LA Woo Daniel D Unverzagt Frederick W FW Safford Monika M Cushman Mary M Limdi Nita N Quarells Rakale R Arnett Donna K DK Irvin Marguerite R MR Zhi Degui D
BMC medical genomics 20190131 Suppl 1
<h4>Background</h4>Cardiovascular disease, diabetes, and kidney disease are among the leading causes of death and disability worldwide. However, knowledge of genetic determinants of those diseases in African Americans remains limited.<h4>Results</h4>In our study, associations between 4956 GWAS catalog reported SNPs and 67 traits were examined among 7726 African Americans from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which is focused on identifying factors that ...[more]
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Project description:BackgroundSickle cell anemia may be associated with cognitive dysfunction, and some complications of sickle cell anemia might affect those with sickle cell trait (SCT), so we hypothesized that SCT is a risk factor for cognitive impairment.MethodsThe Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled a national cohort of 30,239 white and black Americans from 2003 to 7, who are followed every 6 months. Baseline and annual global cognitive function testing used the Six-Item Screener (SIS), a validated instrument (scores range 0-6; ≤ 4 indicates cognitive impairment). Participants with baseline cognitive impairment and whites were excluded. Logistic regression was used to calculate the association of SCT with incident cognitive impairment, adjusted for risk factors. Linear mixed models assessed multivariable-adjusted change in test scores on a biennially administered 3-test battery measuring learning, memory, and semantic and phonemic fluency.FindingsAmong 7743 participants followed for a median of 7·1 years, 85 of 583 participants with SCT (14·6%) developed incident cognitive impairment compared to 902 of 7160 (12·6%) without SCT. In univariate analysis, the odds ratio (OR) of incident cognitive impairment was 1·18 (95% CI: 0·93, 1·51) for those with SCT vs. those without. Adjustment did not impact the OR. There was no difference in change on 3-test battery scores by SCT status (all p > 0·11).InterpretationIn this prospective cohort study of black Americans, SCT was not associated with incident cognitive impairment or decline in test scores of learning, memory and executive function.FundingNational Institutes of Health, American Society of Hematology.
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Project description:We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, between thousands of genetic variants assayed on the Metabochip and hundreds of phenotypes in 5,897 African Americans as part of the Population Architecture using Genomics and Epidemiology (PAGE) I study. The PAGE I study was a National Human Genome Research Institute-funded collaboration of four study sites accessing diverse epidemiologic studies genotyped on the Metabochip, a custom genotyping chip that has dense coverage of regions in the genome previously associated with cardio-metabolic traits and outcomes in mostly European-descent populations. Here we focus on identifying novel phenome-genome relationships, where SNPs are associated with more than one phenotype. To do this, we performed a PheWAS, testing each SNP on the Metabochip for an association with up to 273 phenotypes in the participating PAGE I study sites. We identified 133 putative pleiotropic variants, defined as SNPs associated at an empirically derived p-value threshold of p<0.01 in two or more PAGE study sites for two or more phenotype classes. We further annotated these PheWAS-identified variants using publicly available functional data and local genetic ancestry. Amongst our novel findings is SPARC rs4958487, associated with increased glucose levels and hypertension. SPARC has been implicated in the pathogenesis of diabetes and is also known to have a potential role in fibrosis, a common consequence of multiple conditions including hypertension. The SPARC example and others highlight the potential that PheWAS approaches have in improving our understanding of complex disease architecture by identifying novel relationships between genetic variants and an array of common human phenotypes.
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Project description:BACKGROUND:African Americans are especially at risk of hypertension and dementia. Antihypertensive medications reduce the risk of cardiovascular events, but may also reduce the risk of dementia. OBJECTIVE:To assess the longitudinal effects of antihypertensive medications and blood pressure on the onset of incident dementia in a cohort of African Americans. DESIGN:Prospective cohort. PARTICIPANTS:1236 community-dwelling patients from an inner-city public health care system, aged 65 years and older, with a history of hypertension but no history of dementia, and who had at least three primary care visits and a prescription filled for any medication. MAIN MEASURES:Blood pressure was the average of three seated measurements. Dementia was diagnosed using a two-stage design, with a screening evaluation every 2 to 3 years followed by a comprehensive in-home clinical evaluation for those with a positive screen. Laboratory, inpatient and outpatient encounter data, coded diagnoses and procedures, and medication records were derived from a health information exchange. KEY RESULTS:Of the 1236 hypertensive participants without dementia at baseline, 114 (9%) developed incident dementia during follow-up. Individuals prescribed any antihypertensive medication (n = 816) were found to have a significantly reduced risk of dementia (HR = 0.57, 95% CI 0.37-0.88, p = 0.0114) compared to untreated hypertensive participants (n = 420). When this analysis was repeated including a variable indicating suboptimally treated blood pressure (> 140 mmHg systolic or >90 mmHg diastolic), the effect of antihypertensive medication was no longer statistically significant (HR = 0.65, 95% CI 0.32-1.30, p = 0.2217). CONCLUSIONS:Control of blood pressure in older adult African American patients with hypertension is a key intervention for preventing dementia, with similar benefits from most of the commonly available antihypertensive medications.
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Project description:BackgroundMore inflammation is associated with greater risk incident hypertension, and Black United States (US) adults have excess burden of hypertension. We investigated whether increased inflammation as quantified by higher C-reactive protein (CRP) explains the excess incidence in hypertension experienced by Black US adults.MethodsWe included 6,548 Black and White REasons for Geographic and Racial Differences in Stroke (REGARDS) participants without hypertension at baseline (2003-2007) who attended a second visit (2013-2016). Sex-stratified risk ratios (RRs) for incident hypertension at the second exam in Black compared to White individuals were estimated using Poisson regression adjusted for groups of factors known to partially explain the Black-White differences in incident hypertension. We calculated the percent mediation by CRP of the racial difference in hypertension.ResultsBaseline CRP was higher in Black participants. The Black-White RR for incident hypertension in the minimally adjusted model was 1.33 (95% confidence interval 1.22, 1.44) for males and 1.15 (1.04, 1.27) for females. CRP mediated 6.6% (95% confidence interval 2.7, 11.3%) of this association in females and 19.7% (9.8, 33.2%) in males. In females, CRP no longer mediated the Black-White RR in a model including waist circumference and body mass index, while in males the Black-White difference was fully attenuated in models including income, education and dietary patterns.ConclusionsElevated CRP attenuated a portion of the unadjusted excess risk of hypertension in Black adults, but this excess risk was attenuated when controlling for measures of obesity in females and diet and socioeconomic factors in males. Inflammation related to these risk factors might explain part of the Black-White disparity in hypertension.
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