Assessment of measures of adiposity that correlate with blood pressure among hypertensive Africans

Background: Studies differ on which anthropometric measure of adiposity shows good correlation with cardiovascular diseases. In this study, we evaluated the effects of common epidemiological measures of adiposity as a correlate of elevated blood pressure in an African population.Methodology: The study was carried out between June 2009 and December 2011 at the medical out-patient department of a tertiary healthcare center in Nigeria. Correlation analysis was used to assess the relationship between blood pressure and body mass index (BMI), waist to height ratio (WHtR), and waist circumference (WC).Results: A total of 1,416 Hypertensives comprising 1090 (77%) adult females recruited over two and half years. Women were significantly older (49.2±8.1 vs. 48.0±10.0 years, p=0.039) and shorter (1.6±6.3 vs 1.7±6.8 meters, p<0.0001) when compared with men. Blood pressure parameters were comparable between women and men. Approximately 1 out of 5 participants had good blood pressure control with no gender difference. Anthropometric measurements showed that 446(32%) were overweight, 404(29%) obese and 40(3%) were morbidly obese. Compared with their male counterparts, females were significantly more likely to be obese (P<0.0001). Similarly, 51.6% of the subjects had abdominal obesity, with female preponderance (P<0.0001). Likewise, a greater proportion of women had substantially higher measured waist circumference risk. Compared with other measures of adiposity, body mass index correlated best with diastolic blood pressure in both gender (P< 0.05).Conclusion: This study adds to the evidence that obesity is a major cardiovascular risk factor. BMI, as a measure of adiposity, was found to correlate best with blood pressure. These findings support other observations in other populations that BMI rather than waist to height ratio (WHtR), and waist circumference (WC) is a better correlate of hypertension

Engulfment and cell motility 1 (ELMO1) and apolipoprotein A1 (APOA1) as candidate genes for sickle cell nephropathy

Sickle cell disease (SCD) and apolipoprotein L1 (APOL1) G1/G2 variants increase chronic kidney disease (CKD) risk in African Americans by poorly understood mechanisms. We applied bioinformatics to identify new candidate genes associated with SCD-related CKD. An interaction network demonstrated APOA1 connecting haemoglobin subunit β (HBB) and APOL1 with 36 other candidate genes. Gene expression revealed upregulation of engulfment and cell motility 1 (ELMO1) and downregulation of APOA1 in the kidney cortex of SCD versus non-SCD mice. Analysis of candidate genes identified ELMO1 rs10951509 to be associated with albuminuria and APOA1 rs11216132 with haemoglobinuria in patients with SCD. A bioinformatic approach highlights ELMO1 and APOA1 as potentially associated with SCD nephropathy

Genome-wide association study of kidney function decline in individuals of European descent.

Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.Kidney International advance online publication, 10 December 2014; doi:10.1038/ki.2014.361

Multi-ancestry genome-wide gene–smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene–smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ~18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 X 10 -8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 X 10 -8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2)

Inferences on pod wall and seed defenses against the brown cowpea coreid bug, Clavigralla tometosicollis Stal ( Hempptera Coreidae) in wild and cultivated Vigna species

Published online: 21 Dec 2001Studies were conducted in the laboratory to investigate the different components of the resistance of Vigna vexillata A. Richards, TVnu 72, and several cultivars of cultivated Vigna spp. to infestation and damage by the brown cowpea coreid, Clavigralla tomentosicollis Stäl. The main objective was to determine the different roles of the pod wall and seeds, and the relationship between seed size, number, and damage by this insect. Results showed that both the pod wall and seed clearly contribute different components to the resistance of TVnu 72 to C. tomentosicollis. Analysis of the results suggests that the seed defences and the pod wall pericarp may be more important than are trichomes in this resistance. Seed number was found to influence the extent of damage in a more predictable manner than seed size. However, because both of these traits are generally inversely related and mutually exclusive, their individual effects cannot be completely separated. The implications of these traits in a breeding programme targeted at a specific consumer group are discussed

Medication adherence and blood pressure control: A preliminary assessment of the role of health insurance in Nigeria and Ghana

Objectives: This study sought to assess the current impact of health insurance coverage on medication adherence and blood pressure control of patients being managed for hypertension in Ghana and Nigeria. Methods: The study was a prospective study among 109 patients with hypertension in two health facilities with similar population dynamics in Ghana and Nigeria. Patients were systematically selected, categorized as having health insurance coverage or not, and followed up monthly for 6 months. The outcome variables (medication adherence and blood pressure control) were then measured and compared at 6 months. Analysis was done using Stata with level of significance set at p ⩽ 0.05. Results: There was a 90% insurance coverage among participants from Ghana compared to 15% from Nigeria. National Health Insurance Authority enrolees in both countries had better blood pressure control and medication adherence compared to non-enrolees (adjusted odds ratio = 2.6 and 4.5, respectively). Conclusion: National Health Insurance Authority enrolment was found to be poor among respondents in Nigeria compared to Ghana. Enrolment into the National health financing schemes in both countries led to better blood pressure control and medication adherence among patients with hypertension at primary health facilities. There is therefore the need for system strengthening to improve their sustainability. © The Author(s) 2023.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Meta-analysis of correlated traits via summary statistics from GWASs with an application in hypertension

Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple-even distinct-traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluated together. Such approaches miss the opportunity to systemically integrate the phenome-wide data available for genetic association analysis. In this study, we propose a general approach that can integrate association evidence from summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, which might come from the same or different studies. We allow for trait heterogeneity effects. Population structure and cryptic relatedness can also be controlled. Our simulations suggest that the proposed method has improved statistical power over single-trait analysis in most of the cases we studied. We applied our method to the Continental Origins and Genetic Epidemiology Network (COGENT) African ancestry samples for three blood pressure traits and identified four loci (CHIC2, HOXA-EVX1, IGFBP1/IGFBP3, and CDH17; p &lt; 5.0 × 10(-8)) associated with hypertension-related traits that were missed by a single-trait analysis in the original report. Six additional loci with suggestive association evidence (p &lt; 5.0 × 10(-7)) were also observed, including CACNA1D and WNT3. Our study strongly suggests that analyzing multiple phenotypes can improve statistical power and that such analysis can be executed with the summary statistics from GWASs. Our method also provides a way to study a cross phenotype (CP) association by using summary statistics from GWASs of multiple phenotypes