The effect of mobile health technology on blood pressure control among patients with hypertension in Ghana and Nigeria.

Background: More than half of patients with hypertension in sub-Saharan African do not achieve blood pressure control. This study determined the effect of mobile health technology on systolic blood pressure reduction and blood pressure (BP) control among patients with hypertension in Nigeria and Ghana. Methods: A randomised control trial of 225 adults with hypertension attending two General/Medical Outpatient Clinics each in Nigeria and Ghana was randomized into intervention (n = 116) and control (n = 109) arm respectively. Patients in the intervention arm received messages twice weekly from a mobile app for six months in addition to the usual care while the control arm received usual care only. The study outcomes were systolic blood pressure (SBP) reduction and blood pressure control at six months, while the secondary outcome was medication adherence at six months. Data were collected at 0 and 6 months, it was analysed using SPSS-21 software at a significance level of p < 0.05. Binary logistic regression was used to generate the predictors of good blood pressure control. Results: The mean age for the control and intervention were 60.2 ± 13.5 and 62.6 ± 10.8 years respectively; p-value = 0.300. The intervention group had greater reductions in SBP (-18.7mmHg vs -3.9mmHg; p < 0.001) and greater BP control rate (44.3% vs 24.8%; p-value 0.002). Conclusions: The mobile health intervention resulted in significant SBP reduction rate and improvement in BP control rate in the 6th month. However, improvement in adherence level in the 3rd month and was not sustained in the 6th month. The addition of mobile health technology may be extended for use in the national hypertension control plan. Female gender, formal education and being in the intervention arm were predictors of blood pressure control.

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.

Fibroblast Growth Factor 23 (FGF 23) and intact parathyroid hormone (iPTH) as markers of mineral bone disease among Nigerians with non-diabetic kidney disease.

Background: Excess cardiovascular burden in patients with chronic kidney disease (CKD) has been attributed to the occurrence of CKD-Mineral Bone Disease (CKD - MBD). This study aimed to determine the spectrum of CKD-MBD among Nigerians with CKD using Fibroblast Growth Factor 23 (FGF 23) and intact Parathyroid Hormone (iPTH). Methods: Cross sectional survey of 105 patients with non-diabetic CKD and 104 controls. Information obtained were demographics, aetiology of CKD, features of CKD-MBD. Serum iPTH and FGF 23 were assayed. Results: The mean ages were 48.7±15.3 vs 48.6±17.4 years while 54.7% and 45.2% were males for cases and controls, respectively. The mean plasma FGF 23 (392.8±35.3 vs 133.8±22.7 RU/mL and plasma iPTH (289±25.6 vs 118±10.8 ng/L, respectively. The frequency of elevated FGF 23 (45.7% vs 24.0%, p<0.01) and abnormal iPTH (53.3% vs 14.1%, p- 0.01) were higher in cases. The prevalence of MBD were (59.0% vs 14.4%, p<0.01) in cases and controls while dialysis status OR 2.94, 95% CI (1.2803-5.3645), and elevated FGF 23 OR, 1.87, 95% CI (1.1782-5.4291) were associated with CKD-MBD. Conclusion: The study demonstrated high prevalence of CKD-MBD among patients with non-diabetic CKD while FGF23 and iPTH were useful assays in the diagnosis of CKD-MBD among Nigerians with CKD.

Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies.

Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.

Factors influencing the integration of evidence-based task-strengthening strategies for hypertension control within HIV clinics in Nigeria.

BACKGROUND: Evidence-based task-strengthening strategies for hypertension (HTN) control (TASSH) are not readily available for patients living with HIV in sub-Saharan Africa where the dual burden of HTN and HIV remains high. We are conducting a cluster randomized controlled trial comparing the effectiveness of practice facilitation versus a self-directed control (i.e., receipt of TASSH with no practice facilitation) in reducing blood pressure and increasing the adoption of task-strengthening strategies for HTN control within HIV clinics in Nigeria. Prior to implementing the trial, we conducted formative research to identify factors that may influence the integration of TASSH within HIV clinics in Nigeria. METHODS: This mixed-methods study was conducted with purposively selected healthcare providers at 29 HIV clinics, followed by a 1-day stakeholder meeting with 19 representatives of HIV clinics. We collected quantitative practice assessment data using two instruments: (a) an adapted Service Availability and Readiness Assessment (SARA) tool to assess the capacity of the clinic to manage NCDs and (b) Implementation Climate Scale to assess the degree to which there is a strategic organizational climate supportive of the evidence-based practice implementation. The quantitative data were analyzed using descriptive statistics and measures of scale reliability. We also used the Consolidated Framework for Implementation Research (CFIR), to thematically analyze qualitative data generated and relevant to the aims of this study. RESULTS: Across the 29 clinics surveyed, the focus on TASSH (mean=1.77 (SD=0.59)) and educational support (mean=1.32 (SD=0.68)) subscales demonstrated the highest mean score, with good-excellent internal consistency reliability (Cronbach's alphas ranging from 0.84 to 0.96). Within the five CFIR domains explored, the major facilitators of the intervention included relative advantage of TASSH compared to current practice, compatibility with clinic organizational structures, support of patients' needs, and intervention alignment with national guidelines. Barriers included the perceived complexity of TASSH, weak referral network and patient tracking mechanism within the clinics, and limited resources and diagnostic equipment for HTN. CONCLUSION: Optimizing healthcare workers' implementation of evidence-based TASSH within HIV clinics requires attention to both the implementation climate and contextual factors likely to influence adoption and long-term sustainability. These findings have implications for the development of effective practice facilitation strategies to further improve the delivery and integration of TASSH within HIV clinics in Nigeria. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04704336.

Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.

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 ß (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.

Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline.

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.

The Sickle Cell Disease Ontology: Enabling Collaborative Research and Co-Designing of New Planetary Health Applications.

Sickle cell disease (SCD) is one of the most common blood disorders impacting planetary health. Over 300,000 newborns are diagnosed with SCD each year globally, with an increasing trend. The sickle cell disease ontology (SCDO) is the most comprehensive multidisciplinary SCD knowledge portal. The SCDO was collaboratively developed by the SCDO working group, which includes experts in SCD and data standards from across the globe. This expert review presents highlights and lessons learned from the fourth SCDO workshop that marked the beginning of applications toward planetary health impact, and with an eye to empower and cultivate multisite SCD collaborative research. The workshop was organized by the Sickle Africa Data Coordinating Center (SADaCC) and attended by 44 participants from 14 countries, with 2 participants connecting remotely. Notably, from the standpoint of democratizing and innovating scientific meeting design, an SCD patient advocate also presented at the workshop, giving a broader real-life perspective on patients' aspirations, needs, and challenges. A major component of the workshop was new approaches to harness SCDO to harmonize data elements used by different studies. This was facilitated by a web-based platform onto which participants uploaded data elements from previous or ongoing SCD-relevant research studies before the workshop, making multisite collaborative research studies based on existing SCD data possible, including multisite cohort, SCD global clinical trials, and SCD community engagement approaches. Trainees presented proposals for systematic literature reviews in key SCD research areas. This expert review emphasizes potential and prospects of SCDO-enabled data standards and harmonization to facilitate large-scale global SCD collaborative initiatives. As the fields of public and global health continue to broaden toward planetary health, the SCDO is well poised to play a prominent role to decipher SCD pathophysiology further, and co-design diagnostics and therapeutics innovation in the field.

Association of HSD17B13 rs72613567:TA with non-alcoholic fatty liver disease in Hispanics/Latinos.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) disproportionately affects Hispanic/Latinos and rates of NAFLD vary among Hispanics from different background groups. Genetic variants and continental ancestry contribute to NAFLD disparities among Hispanics. We evaluated two newly identified NAFLD-associated single nucleotide polymorphisms of HSD17B13, rs72613567:TA and rs62305723:A in Hispanics/Latinos. METHODS: Clinical data, genotypes of variants of interest and estimates of continental ancestry were extracted from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) database, which includes a cohort of 16 415 US Hispanic/Latinos. Surrogate endpoints for NAFLD were suspected NAFLD based on unexplained aminotransferase elevation, continuous ALT levels and FIB-4 scores to estimate hepatic fibrosis. RESULTS: In all, 9342 participants were included for analysis. The rs72613567:TA allele was found in 15.3% and the rs62305723:A allele was identified in 4.5% of HCHS/SOL participants. rs72613567:TA was less frequent in persons with vs without suspected NAFLD (12.4% vs 15.7%, P < .001) and rs72613567:TA was associated with lower FIB-4 scores (P = .01). For persons with the NAFLD-associated PNPLA3 rs738409:G allele, the presence of rs72613567:TA was associated with a lower rate of suspected NAFD (odds ratio = 0.76, P < .001). rs72613567:TA was less frequent in Hispanic/Latino background groups with higher rates of suspected NAFLD. The rs62305723:A allele was not associated with suspected NAFLD or FIB-4 score. CONCLUSION: The rs72613567:TA allele is associated with lower rates of suspected NAFLD and lower FIB-4 scores among Hispanic/Latinos and with lower rates of suspected NAFLD in persons with the PNPLA3 rs738409:G allele. The rs72613567:TA allele contributes to NAFLD disparities among Hispanic/Latino background groups.

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria.

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

A catalog of genetic loci associated with kidney function from analyses of a million individuals.

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

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.

American Ancestry Is a Risk Factor for Suspected Nonalcoholic Fatty Liver Disease in Hispanic/Latino Adults.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) disproportionally affects Hispanic/Latino populations. However, the magnitude varies among Hispanic/Latino ethnic groups. We investigated the mechanisms of these disparities. METHODS: We examined associations of NAFLD-associated genetic variants and continental ancestry with suspected NAFLD, levels of alanine aminotransferase (ALT), and liver fibrosis using data from the Hispanic Community Health Study/Study of Latinos-a population-based study of Hispanic/Latino adults in the United States. We evaluated data from 16,415 Hispanic/Latino adults in 4 cities from 2008 through 2011. Subjects suspected of having NAFLD or liver fibrosis were identified based on unexplained increases in levels of aminotransferases and FIB-4 score, respectively. RESULTS: Among the 9342 participants with available genetic and aminotransferase data, the PNPLA3 G allele (odds ratio [OR], 1.53; 95% CI, 1.41-1.66), TM6SF2 T allele (OR, 1.41; 95% CI, 1.20-1.67), and PPP1R3B G allele (OR, 1.16; 95% CI, 1.06-1.28) were associated with suspected NAFLD. PNPLA3 G was also associated with increased levels of ALT, except in participants with Dominican and South American backgrounds, and with liver fibrosis. The frequency of PNPLA3 G was high (41%) and TM6SF2 T (5%) was low in Hispanic/Latinos. PNPLA3 G frequency differed among Hispanic background groups with the highest proportion in Mexicans (52%) and the lowest proportion in Dominicans (23%). After adjustment for demographic, clinical, and behavioral factors, as well as PNPLA3 G, TM6SF2 T, and PPP1R3B G, American ancestry had a positive association with level of ALT (r = 6.61%; P < .001), whereas African (r = -3.84%; P < .001) and European (r = -4.31%; P < .001) ancestry were inversely associated with level of ALT. CONCLUSIONS: American ancestry and PNPLA3 G are independent predictors of ALT levels in US Hispanic/Latinos and may in part explain NAFLD disparities in US Hispanic/Latinos.

Combined linkage and association analysis identifies rare and low frequency variants for blood pressure at 1q31.

High blood pressure (BP) is a major risk factor for cardiovascular disease (CVD) and is more prevalent in African Americans as compared to other US groups. Although large, population-based genome-wide association studies (GWAS) have identified over 300 common polymorphisms modulating inter-individual BP variation, largely in European ancestry subjects, most of them do not localize to regions previously identified through family-based linkage studies. This discrepancy has remained unexplained despite the statistical power differences between current GWAS and prior linkage studies. To address this issue, we performed genome-wide linkage analysis of BP traits in African-American families from the Family Blood Pressure Program (FBPP) and genotyped on the Illumina Human Exome BeadChip v1.1. We identified a genomic region on chromosome 1q31 with LOD score 3.8 for pulse pressure (PP), a region we previously implicated in DBP studies of European ancestry families. Although no reported GWAS variants map to this region, combined linkage and association analysis of PP identified 81 rare and low frequency exonic variants accounting for the linkage evidence. Replication analysis in eight independent African ancestry cohorts (N = 16,968) supports this specific association with PP (P = 0.0509). Additional association and network analyses identified multiple potential candidate genes in this region expressed in multiple tissues and with a strong biological support for a role in BP. In conclusion, multiple genes and rare variants on 1q31 contribute to PP variation. Beyond producing new insights into PP, we demonstrate how family-based linkage and association studies can implicate specific rare and low frequency variants for complex traits.

White Paper: Pathways to Progress in Newborn Screening for Sickle Cell Disease in Sub-Saharan Africa.

Sickle Cell Disease (SCD) is among the most common single-gene diseases in the world but evidence-based comprehensive health care has not been implemented where the highest prevalence of SCD occurs, in sub-Saharan Africa (SSA). It represents an urgent health burden, both in terms of mortality and morbidity with an estimated mortality of 8-16% in children under 5 years in SSA. Addressing the high mortality of SCD in SSA and for effective management of SCD, newborn screening (NBS) should be incorporated with prevention of infections (including pneumococcal septicaemia and malaria), parental education and support at all levels of healthcare provision to enable timely recognition. The NBS working group of the Africa Sickle Cell Research Network (AfroSickleNet) collaboration surveyed current projects in NBS in SSA, and current conditions that hinder more widespread implementation of NBS for SCD. Solutions based on new point-of-care testing technology to disseminate education, and implementation science approaches that leverage existing resources are proposed.

Sickle Cell Disease Clinical Trials and Phenotypes.

Sickle cell disease, one of the world's most common genetic disorders is prevalent in sub-Saharan Africa. The trans-Atlantic slave trade accounted for the gene movement from Africa to the Caribbean and United States of America and lately, migration has resulted in the introduction of the gene to the United Kingdom and other parts of Europe. Different haplotypes exist, however the differences in these haplotypes are not sufficient to explain the different clinical variations within the same region or different settings.

Correction: Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

[This corrects the article DOI: 10.1371/journal.pgen.1006728.].