A Genome-wide study of blood pressure in African Americans accounting for gene-smoking interaction.

Cigarette smoking has been shown to be a health hazard. In addition to being considered a negative lifestyle behavior, studies have shown that cigarette smoking has been linked to genetic underpinnings of hypertension. Because African Americans have the highest incidence and prevalence of hypertension, we examined the joint effect of genetics and cigarette smoking on health among this understudied population.

Comprehensive evaluation of AmpliSeq transcriptome, a novel targeted whole transcriptome RNA sequencing methodology for global gene expression analysis.

Background: Whole transcriptome sequencing (RNA-seq) represents a powerful approach for whole transcriptome gene expression analysis. However, RNA-seq carries a few limitations, e.g.

Multilingual Validation of the Questionnaire for Verifying Stroke-Free Status in West Africa.

Background And Purpose: The Questionnaire for Verifying Stroke-Free Status (QVSFS), a method for verifying stroke-free status in participants of clinical, epidemiological, and genetic studies, has not been validated in low-income settings where populations have limited knowledge of stroke symptoms. We aimed to validate QVSFS in 3 languages, Yoruba, Hausa and Akan, for ascertainment of stroke-free status of control subjects enrolled in an on-going stroke epidemiological study in West Africa.

Methods: Data were collected using a cross-sectional study design where 384 participants were consecutively recruited from neurology and general medicine clinics of 5 tertiary referral hospitals in Nigeria and Ghana.

Archeological Echocardiography: Digitization and Speckle Tracking Analysis of Archival Echocardiograms in the HyperGEN Study.

Background: Several large epidemiologic studies and clinical trials have included echocardiography, but images were stored in analog format and these studies predated tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE). We hypothesized that digitization of analog echocardiograms, with subsequent quantification of cardiac mechanics using STE, is feasible, reproducible, accurate, and produces clinically valid results.

Methods: In the NHLBI HyperGEN study (N = 2234), archived analog echocardiograms were digitized and subsequently analyzed using STE to obtain tissue velocities/strain.

The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter.

Scope: Omega-3 PUFAs (n-3 PUFAs) reduce IL-6 gene expression, but their effects on transcription regulatory mechanisms are unknown. We aimed to conduct an integrated analysis with both population and in vitro studies to systematically explore the relationships among n-3 PUFA, DNA methylation, single nucleotide polymorphisms (SNPs), gene expression, and protein concentration of IL6.

Methods And Results: Using data in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study and the Encyclopedia of DNA Elements (ENCODE) consortium, we found that higher methylation of IL6 promoter cg01770232 was associated with higher IL-6 plasma concentration (p = 0.

Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium.

Background: Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.

Lipid changes due to fenofibrate treatment are not associated with changes in DNA methylation patterns in the GOLDN study.

Fenofibrate lowers triglycerides (TG) and raises high density lipoprotein cholesterol (HDLc) in dyslipidemic individuals. Several studies have shown genetic variability in lipid responses to fenofibrate treatment. It is, however, not known whether epigenetic patterns are also correlated with the changes in lipids due to fenofibrate treatment.

Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians.

Background: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown.

Objective: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus.

Phenotyping Stroke in Sub-Saharan Africa: Stroke Investigative Research and Education Network (SIREN) Phenomics Protocol.

Background: As the second leading cause of death and the leading cause of adult-onset disability, stroke is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur, and stroke burden is projected to increase in the coming decades. However, traditional and emerging risk factors for stroke in SSA have not been well characterized, thus limiting efforts at curbing its devastating toll. The Stroke Investigative Research and Education Network (SIREN) project is aimed at comprehensively evaluating the key environmental and genomic risk factors for stroke (and its subtypes) in SSA while simultaneously building capacities in phenomics, biobanking, genomics, biostatistics, and bioinformatics for brain research.

Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN).

Objective: The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variants through a genome-wide association (GWA) study in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN).

Left ventricular hypertrophy after hypertensive pregnancy disorders.

Objective: Cardiac changes of hypertensive pregnancy include left ventricular hypertrophy (LVH) and diastolic dysfunction. These are thought to regress postpartum. We hypothesised that women with a history of hypertensive pregnancy would have altered LV geometry and function when compared with women with only normotensive pregnancies.

Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.

The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine-dependent cases (Fagerström Test for Nicotine Dependence score⩾4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (minor allele frequency (MAF)⩾0.

The role of genetic variants in CRP in radiographic severity in African Americans with early and established rheumatoid arthritis.

This study investigates the association of CRP (C-reactive protein) single-nucleotide polymorphisms (SNPs) with plasma CRP levels and radiographic severity in African Americans with early and established rheumatoid arthritis (RA). Using a cross-sectional case-only design, CRP SNPs were genotyped in two independent sets of African Americans with RA: Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR 1) and CLEAR 2. Radiographic data and CRP measurements were available for 294 individuals from CLEAR 1 (median (interquartile range (IQR) 25-75) disease duration of 1 (0.

A family-specific linkage analysis of blood lipid response to fenofibrate in the Genetics of Lipid Lowering Drug and Diet Network.

Cost-effective identification of novel pharmacogenetic variants remains a pressing need in the field. Using data from the Genetics of Lipid Lowering Drugs and Diet Network, we identified genomic regions of relevance to fenofibrate response in a sample of 173 families. Our approach included a multipoint linkage scan, followed by selection of the families showing evidence of linkage.

Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference.

Objective: To conduct an epigenome-wide analysis of DNA methylation and obesity traits.

Methods: DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled.

Clock Genes Explain a Large Proportion of Phenotypic Variance in Systolic Blood Pressure and This Control Is Not Modified by Environmental Temperature.

Background: Diurnal variation in blood pressure (BP) is regulated, in part, by an endogenous circadian clock; however, few human studies have identified associations between clock genes and BP. Accounting for environmental temperature may be necessary to correct for seasonal bias.

Methods: We examined whether environmental temperature on the day of participants' assessment was associated with BP, using adjusted linear regression models in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) (n = 819) and the Boston Puerto Rican Health Study (BPRHS) (n = 1,248) cohorts.

Race influences warfarin dose changes associated with genetic factors.

Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor, thereby attenuating the differential effect by race. Attenuation likely occurs in both race groups but may be more pronounced in the less-represented race group. Therefore, we evaluated whether the effect of clinical (age, body surface area [BSA], chronic kidney disease [CKD], and amiodarone use) and genetic factors (CYP2C9*2, *3, *5, *6, *11, rs12777823, VKORC1, and CYP4F2) on warfarin dose differs by race using regression analyses among 1357 patients enrolled in a prospective cohort study and compared predictive ability of race-combined vs race-stratified models.

Stroke genomics in people of African ancestry: charting new paths.

One in six people worldwide will experience a stroke in his/her lifetime. While people in Africa carry a disproportionately higher burden of poor stroke outcomes, compared to the rest of the world, the exact contribution of genomic factors to this disparity is unknown. Despite noteworthy research into stroke genomics, studies exploring the genetic contribution to stroke among populations of African ancestry in the United States are few.

The burden of stroke in Africa: a glance at the present and a glimpse into the future.

Objective: Information on the current burden of stroke in Africa is limited. The aim of this review was to comprehensively examine the current and projected burden of stroke in Africa.

Methods: We systematically reviewed the available literature (PubMed and AJOL) from January 1960 and June 2014 on stroke in Africa.

Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci.

Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are dysregulated in numerous conditions. The Illumina 450K Bead Chip array was used to assay DNA methylation in leukocyte DNA obtained from 2097 African American adults in the Atherosclerosis Risk in Communities (ARIC) study.