A Genome-Wide Association Study of Hypertension and Blood Pressure in African Americans

The evidence for the existence of genetic susceptibility variants for the common form of hypertension (“essential hypertension”) remains weak and inconsistent. We sought genetic variants underlying blood pressure (BP) by conducting a genome-wide association study (GWAS) among African Americans, a population group in the United States that is disproportionately affected by hypertension and associated complications, including stroke and kidney diseases. Using a dense panel of over 800,000 SNPs in a discovery sample of 1,017 African Americans from the Washington, D.C., metropolitan region, we identified multiple SNPs reaching genome-wide significance for systolic BP in or near the genes: PMS1, SLC24A4, YWHA7, IPO7, and CACANA1H. Two of these genes, SLC24A4 (a sodium/potassium/calcium exchanger) and CACNA1H (a voltage-dependent calcium channel), are potential candidate genes for BP regulation and the latter is a drug target for a class of calcium channel blockers. No variant reached genome wide significance for association with diastolic BP (top scoring SNP rs1867226, p = 5.8×10−7) or with hypertension as a binary trait (top scoring SNP rs9791170, p = 5.1×10−7). We replicated some of the significant SNPs in a sample of West Africans. Pathway analysis revealed that genes harboring top-scoring variants cluster in pathways and networks of biologic relevance to hypertension and BP regulation. This is the first GWAS for hypertension and BP in an African American population. The findings suggests that, in addition to or in lieu of relying solely on replicated variants of moderate-to-large effect reaching genome-wide significance, pathway and network approaches may be useful in identifying and prioritizing candidate genes/loci for further experiments

Maladies et plantes vasculaires du Karité (Vitellaria paradoxa Gaertn) au Bénin

La présente étude vise à évaluer les maladies et les plantes vasculaires du karité (Vitellaria paradoxa C. F. Gaertn) dans les savanes Soudanienne (SS) et Nord guinéenne (SNG) du Bénin. Pour ce faire, quarante sites au total ont été prospectés au cours du mois de juillet 2018. Sur chaque site, l’incidence et la sévérité des symptômes de maladies, la densité et la distribution des plantes vasculaires ont été étudiées. Des échantillons de feuilles malades, des plantes vasculaires du karité ont été prélevés pour lʼidentification au laboratoire. Lasiodiplodia theobromae, Colletotrichum gloeosporioides, Pestalotiopsis sp, Xanthomonas sp ont été les agents pathogènes identifiés. Les valeurs d’incidence étaient élevées dans la SS (59,6% L. theobromae, et de 42,2% Xanthomonas sp) et dans la SNG (67,5% Pestalotiopsis sp et de 55% L. theobromae). Les valeurs de sévérité étaient élevées dans la SS (39% L. theobromae et de 30,6% Xanthomonas sp) et dans la SNG (54,7% Pestalotiopsis sp et 43% L. theobromae). Les données collectées sur la densité des plantes vasculaires ont montré une Orchidiaceae holo-épiphyte (Calyptrochilum christyanum), une Moraceae hémi-épiphyte (Ficus thonningii), une Renonculaceae (Alafia barteri) et deux Loranthaceae (Tapinanthus dodoneifolius, Tapinanthus globiferus). T. dodoneifolius et T. globiferus sont plus répandus avec des taux d’infestation moyens respectifs de 68,67% et de 66,58% et des densités moyennes par plant respectives de 5,64 touffes et de 2,52 touffes. Ainsi, les efforts d’amélioration de la production de karité doivent prendre en compte les stratégies de lutte contre ces agents pathogènes et plantes vasculaires.   The present study aims to assess diseases and vascular plants of the shea-butter tree (Vitellaria paradoxa C. F. Gaertn) in Sudan Savanna (SS) and Northern Guinea Savanna (NGS) of Benin. Thus, forty (40) sites in total were surveyed in July 2018. On each site, incidence and severity of the disease symptoms, and density and distribution of vascular plants of the shea-butter tree were studied. Samples of diseased leaves and vascular plants of the sheabutter tree were collected for laboratory identification. The pathogens Lasiodiplodia theobromae, Colletotrichum gloeosporioides, Pestalotiopsis sp) and Xanthomonas sp were identified. The incidence values were high in SS (59.6% L. theobromae and 42.2% Xanthomonas sp) and in NGS (67.5% Pestalotiopsis sp and 55% L. theobromae). The severity values were high in SS (39% L. theobromae and 30.6% Xanthomonas sp) and in NGS (54.7% Pestalotiopsis sp and 43% L. theobromae). Data collected on the density of vascular plants of the shea-butter tree showed one holo-epiphytic Orchidiaceae (Calyptrochilum christyanum), one Moraceae (Ficus thonningii), one Renonculaceae (Alafia barteri) and two Loranthaceae (Tapinanthus dodoneifolius, Tapinanthus globiferus). T. dodoneifolius and T. globiferus were more widespread with respectively infestation rate of 68.67% and 66.58%, and respectively average densities per shea plant of 5.64 tufts and 2.52 tufts. Thus, efforts to improve shea-butter production must take into account strategies for disease pathogens and vacular plants control in the sheabutter parklands in Benin

RPS19 and TYMS SNPs and Prevalent High Risk Human Papilloma Virus Infection in Nigerian Women

High risk HPV (hrHPV) infection is a necessary cause of cervical cancer but the host genetic determinants of infection are poorly understood. We enrolled 267 women who presented to our cervical cancer screening program in Abuja, Nigeria between April 2012 and August 2012. We collected information on demographic characteristics, risk factors of cervical cancer and obtained samples of blood and cervical exfoliated cells from all participants. We used Roche Linear Array HPV Genotyping Test® to characterize the prevalent HPV according to manufacturer's instruction; Sequenom Mass Array to test 21 SNPs in genes/regions previously associated with hrHPV and regression models to examine independent factors associated with HPV infection. We considered a p<0.05 as significant because this is a replication study. There were 65 women with and 202 women without hrHPV infection. Under the allelic model, we found significant association between two SNPs, rs2305809 on RPS19 and rs2342700 on TYMS, and prevalent hrHPV infection. Multivariate analysis of hrHPV risk adjusted for age, body mass index, smoking, age of menarche, age at sexual debut, lifetime total number of sexual partners and the total number of pregnancies as covariates, yielded a p-value of 0.071 and 0.010 for rs2305809 and rs2342700, respectively. Our findings in this unique population suggest that a number of genetic risk variants for hrHPV are shared with other population groups. Definitive studies with larger sample sizes and using genome wide approaches are needed to understand the genetic architecture of hrHPV risk in multiple populations

Development of admixture mapping panels for African Americans from commercial high-density SNP arrays

<p>Abstract</p> <p>Background</p> <p>Admixture mapping is a powerful approach for identifying genetic variants involved in human disease that exploits the unique genomic structure in recently admixed populations. To use existing published panels of ancestry-informative markers (AIMs) for admixture mapping, markers have to be genotyped <it>de novo </it>for each admixed study sample and samples representing the ancestral parental populations. The increased availability of dense marker data on commercial chips has made it feasible to develop panels wherein the markers need not be predetermined.</p> <p>Results</p> <p>We developed two panels of AIMs (~2,000 markers each) based on the Affymetrix Genome-Wide Human SNP Array 6.0 for admixture mapping with African American samples. These two AIM panels had good map power that was higher than that of a denser panel of ~20,000 random markers as well as other published panels of AIMs. As a test case, we applied the panels in an admixture mapping study of hypertension in African Americans in the Washington, D.C. metropolitan area.</p> <p>Conclusions</p> <p>Developing marker panels for admixture mapping from existing genome-wide genotype data offers two major advantages: (1) no <it>de novo </it>genotyping needs to be done, thereby saving costs, and (2) markers can be filtered for various quality measures and replacement markers (to minimize gaps) can be selected at no additional cost. Panels of carefully selected AIMs have two major advantages over panels of random markers: (1) the map power from sparser panels of AIMs is higher than that of ~10-fold denser panels of random markers, and (2) clusters can be labeled based on information from the parental populations. With current technology, chip-based genome-wide genotyping is less expensive than genotyping ~20,000 random markers. The major advantage of using random markers is the absence of ascertainment effects resulting from the process of selecting markers. The ability to develop marker panels informative for ancestry from SNP chip genotype data provides a fresh opportunity to conduct admixture mapping for disease genes in admixed populations when genome-wide association data exist or are planned.</p

African Ancestry Gradient Is Associated with Lower Systemic F 2

Context. Low levels of systemic F2-isoprostanes (F2-IsoP) increase the risk of diabetes and weight gain and were found in African Americans. Low F2-IsoPs could reflect an unfavorable metabolic characteristic, namely, slow mitochondrial metabolism in individuals with African ancestry. Objective. To examine differences in plasma F2-IsoPs in three groups with a priori different proportion of African ancestry: non-Hispanic Whites (NHWs), US-born African Americans (AAs), and West African immigrants (WAI). Design. Cross-sectional study. Setting. Georgia residents recruited from church communities. Participants. 218 males and females 25–74 years of age, who are self-identified as NHW (n=83), AA (n=56), or WAI (n=79). Main Outcome Measure(s). Plasma F2-IsoPs quantified by gas chromatography-mass spectrometry. Results. After adjustment for age, gender, obesity, and other comorbidities, WAI had lower levels of plasma F2-IsoP than AA (beta-coefficient = −9.8, p<0.001) and AA had lower levels than NHW (beta-coefficient = −30.3, p<0.001). Similarly, among healthy nonobese participants, F2-IsoP levels were lowest among WAI, followed by AA, and the highest levels were among NHW. Conclusion. Plasma F2-IsoPs are inversely associated with African ancestry gradient. Additional studies are required to test whether optimization of systemic F2-IsoP levels can serve as means to improve race-specific lifestyle and pharmacological intervention targeted to obesity prevention and treatment

<i>HLA</i> and autoantibodies define scleroderma subtypes and risk in African and European Americans and suggest a role for molecular mimicry

Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examined HLA associations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominant HLA-DRB1*08:04 and HLA-DRB1*11:02 alleles were associated with overall SSc risk, and the HLA-DRB1*08:04 allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.4). These African ancestry-predominant alleles may help explain the increased frequency and severity of SSc among the AA population. In the EA population, the HLA-DPB1*13:01 and HLA-DRB1*07:01 alleles were more strongly associated with antitopoisomerase (ATA) and anticentromere antibody-positive subsets of SSc, respectively, than with overall SSc risk, emphasizing the importance of HLA in defining autoantibody subtypes. The association of the HLA-DPB1*13:01 allele with the ATA+ subset of SSc in both AA and EA patients demonstrated a transancestry effect. A direct correlation between SSc prevalence and HLA-DPB1*13:01 allele frequency in multiple populations was observed (r = 0.98, P = 3 × 10−6). Conditional analysis in the autoantibody subsets of SSc revealed several associated amino acid residues, mostly in the peptide-binding groove of the class II HLA molecules. Using HLA &#x3B1; / &#x3B2; allelic heterodimers, we bioinformatically predicted immunodominant peptides of topoisomerase 1, fibrillarin, and centromere protein A and discovered that they are homologous to viral protein sequences from the Mimiviridae and Phycodnaviridae families. Taken together, these data suggest a possible link between HLA alleles, autoantibodies, and environmental triggers in the pathogenesis of SSc

ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response.

Genome analysis of diverse human populations has contributed to the identification of novel genomic loci for diseases of major clinical and public health impact. Here, we report a genome-wide analysis of type 2 diabetes (T2D) in sub-Saharan Africans, an understudied ancestral group. We analyze ~18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana and Kenya. We identify a previously-unreported genome-wide significant locus: ZRANB3 (Zinc Finger RANBP2-Type Containing 3, lead SNP p = 2.831 × 10-9). Knockdown or genomic knockout of the zebrafish ortholog results in reduction in pancreatic β-cell number which we demonstrate to be due to increased apoptosis in islets. siRNA transfection of murine Zranb3 in MIN6 β-cells results in impaired insulin secretion in response to high glucose, implicating Zranb3 in β-cell functional response to high glucose conditions. We also show transferability in our study of 32 established T2D loci. Our findings advance understanding of the genetics of T2D in non-European ancestry populations

Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldWe recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism