Browsing by Author "Adebamowo, C."
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Item C-reactive protein (CRP) promoter polymorphisms influence circulating CRP levels in a genome-wide association study of African Americans(Human Molecular Genetics, 2012-07) Doumatey, A.P.; Chen, G.; Ayele, F.T.; Zhou, J.; Erdos, M.; Shriner, D.; Huang, H.; Adeleye, J.; Balogun, W.; Fasanmade, O.; Johnson, T.; Oli, J.; Okafor, G.; Amoah, A.; Eghan, B.A.; Agyenim-Boateng, K.; Acheampong, J.; Adebamowo, C.; Gerry, N.P.; Christman, M.F.; Adeyemo, A.; Rotimi, C.N.C-reactive protein (CRP) is an acute phase reactant protein produced primarily by the liver. Circulating CRP levels are influenced by genetic and non-genetic factors, including infection and obesity. Genome-wide association studies (GWAS) provide an unbiased approach towards identifying loci influencing CRP levels. None of the six GWAS for CRP levels has been conducted in an African ancestry population. The present study aims to: (i) identify genetic variants that influence serum CRP in African Americans (AA) using a genome-wide association approach and replicate these findings in West Africans (WA), (ii) assess transferability of major signals for CRP reported in European ancestry populations (EA) to AA and (iii) use the weak linkage disequilibrium (LD) structure characteristic of African ancestry populations to fine-map the previously reported CRP locus. The discovery cohort comprised 837 unrelated AA, with the replication of significant single-nucleotide polymorphisms (SNPs) assessed in 486 WA. The association analysis was conducted with 2 366 856 genotyped and imputed SNPs under an additive genetic model with adjustment for appropriate covariates. Genome-wide and replication significances were set at P < 5 × 10-8 and P < 0.05, respectively. Ten SNPs in (CRP pseudogene-1) CRPP1 and CRP genes were associated with serum CRP (P = 2.4 × 10-09 to 4.3 × 10-11). All but one of the top-scoring SNPs associated with CRP in AA were successfully replicated in WA. CRP signals previously identified in EA samples were transferable to AAs, and we were able to fine-map this signal, reducing the region of interest from the 25 kb of LD around the locus in the HapMap CEU sample to only 8 kb in our AA sample.Item Circulating adiponectin is associated with renal function independent of age and serum lipids in West Africans(International Journal of Nephrology, 2012) Doumatey, A.P.; Zhou, J.; Huang, H.; Adeleye, J.; Balogun, W.; Fasanmade, O.; Johnson, T.; Oli, J.; Okafor, G.; Amoah, A.; Eghan, B.; Agyenim-Boateng, K.; Acheampong, J.; Adebamowo, C.; Adeyemo, A.; Rotimi, C.N.Adiponectin, a protein secreted by adipose tissue, has been associated with renal dysfunction. However, these observations have not been adequately investigated in large epidemiological studies of healthy individuals in general and in African populations in particular. Hence, we designed this study to evaluate the relationship between adiponectin and renal function in a large group of nondiabetic West Africans. Total adiponectin was measured in 792 participants. MDRD and Cockroft-Gault (CG-) estimated GFR were used as indices of renal function. Linear and logistic regression models were used to determine the relationship between adiponectin and renal function. Adiponectin showed an inverse relationship with eGFR in univariate (Beta MDRD = - 0.18, Beta CG = - 0.26) and multivariate (Beta MDRD = - 0.10, Beta CG = - 0.09) regression analyses. The multivariate models that included age, sex, BMI, hypertension, smoking, HDL-C, LDL-C, triglycerides, and adiponectin explained 30 and 55.6 of the variance in GFR estimated by MDRD and CG methods, respectively. Adiponectin was also a strong predictor of moderate chronic kidney disease (defined as eGFR 60 mL/min/1.73 m 2). We demonstrate that adiponectin is associated with renal function in nondiabetic West Africans. The observed relationship is independent of age and serum lipids. Our findings suggest that adiponectin may have clinical utility as a biomarker of renal function.Item Data Resource Profile: Cardiovascular H3Africa Innovation Resource (CHAIR)(International Journal of Epidemiology, 2019-04-01) Adu, D.; Owolabi, M.O.; Akpa, O.M.; Made, F.; Adebamowo, S.N.; Ojo, A.; Motala, A.A.; Mayosi, B.M.; Ovbiagele, B.; Adebamowo, C.; Tayo, B.; Rotimi, C.; Akinyemi, R.; Gebregziabher, M.; Sarfo, F.; Wahab, K.W.; Parekh, R.S.; Engel, M.E.; Chisala, C.; Peprah, E.; Mensah, G.; Wiley, K.; Troyer, J.; Ramsay, M.Low- and middle-income countries (LMIC) constitute the majority of the world’s population and bear more than 80% of the global burden of cardiovascular disease (CVD).1,2 The recent increases in CVD globally are also reflected in LMIC, where the prevalence of overall deaths from CVD was 28% in 20013 and premature CVD mortality was 37% in 2015.4 The paucity of data regarding the drivers of the CVD epidemic and contextualized solutions is, in part, because less than 10% of the global research resources and facilities for implementation are found in LMIC.5,6 Therefore LMIC are particularly disadvantaged in dealing with the CVD burden with targeted interventions. at the individual and community levels. due to the lack of data availability.Item Evaluation of genome wide association study associated type 2 diabetes susceptibility loci in sub Saharan Africans(Frontiers in Genetics, 2015-11) Adeyemo, A.A.; Tekola-Ayele, F.; Doumatey, A.P.; Bentley, A.R.; Chen, G.; Huang, H.; Zhou, J.; Shriner, D.; Fasanmade, O.; Okafor, G.; Eghan, B.Jr.; Agyenim-Boateng, K.; Adeleye, J.; Balogun, W.; Elkahloun, A.; Chandrasekharappa, S.; Owusu, S.; Amoah, A.; Acheampong, J.; Johnson, T.; Oli, J.; Adebamowo, C.; Collins, F.; Dunston, G.; Rotimi, C.N.Genome wide association studies (GWAS) for type 2 diabetes (T2D) undertaken in European and Asian ancestry populations have yielded dozens of robustly associated loci. However, the genomics of T2D remains largely understudied in sub-Saharan Africa (SSA), where rates of T2D are increasing dramatically and where the environmental background is quite different than in these previous studies. Here, we evaluate 106 reported T2D GWAS loci in continental Africans. We tested each of these SNPs, and SNPs in linkage disequilibrium (LD) with these index SNPs, for an association with T2D in order to assess transferability and to fine map the loci leveraging the generally reduced LD of African genomes. The study included 1775 unrelated Africans (1035 T2D cases, 740 controls; mean age 54 years; 59% female) enrolled in Nigeria, Ghana, and Kenya as part of the Africa America Diabetes Mellitus (AADM) study. All samples were genotyped on the Affymetrix Axiom PanAFR SNP array. Forty-one of the tested loci showed transferability to this African sample (p < 0.05, same direction of effect), 11 at the exact reported SNP and 30 others at SNPs in LD with the reported SNP (after adjustment for the number of tested SNPs). TCF7L2 SNP rs7903146 was the most significant locus in this study (p = 1.61 × 10-8). Most of the loci that showed transferability were successfully fine-mapped, i.e., localized to smaller haplotypes than in the original reports. The findings indicate that the genetic architecture of T2D in SSA is characterized by several risk loci shared with non-African ancestral populations and that data from African populations may facilitate fine mapping of risk loci. The study provides an important resource for meta-analysis of African ancestry populations and transferability of novel loci. © 2015 Adeyemo, Tekola-Ayele, Doumatey, Bentley, Chen, Huang, Zhou, Shriner, Fasanmade, Okafor, Eghan, Agyenim-Boateng, Adeleye, Balogun, Elkahloun, Chandrasekharappa, Owusu, Amoah, Acheampong, Johnson, Oli, Adebamowo, Collins, Dunston and Rotimi.Item Low HDL-cholesterol with normal triglyceride levels is the most common lipid pattern in West Africans and African Americans with metabolic syndrome: Implications for cardiovascular disease prevention(CVD Prevention and Control, 2010-09) Sumner, A.E.; Zhou, J.; Doumatey, A.; Imoisili, O.E.; Amoah, A.; Acheampong, J.; Oli, J.; Johnson, T.; Adebamowo, C.; Rotimi, C.N.Background: Although designed to predict cardiovascular disease and type 2 diabetes mellitus, the Metabolic Syndrome (MetSyn) under-predicts these conditions in African Americans (AA). Failure of MetSyn in AA is often attributed to their relative absence of hypertriglyceridemia. It is unknown if the African experience with MetSyn will be similar or different to that in AA. Focusing on the lipid profile, our goal was to determine in West Africans (WA) and AA the pattern of variables that leads to the diagnosis of the MetSyn. Methods: Cross-sectional analysis of 1296 subjects (364 WA, 44% male, 932 AA, 46% male). WA were from urban centers in Nigeria and Ghana and enrolled in the Africa America Diabetes Mellitus Study. AA lived in Washington, DC and participated in the Howard University Family Study. Results: The prevalence of MetSyn was different in WA women and men: 42% vs.19%, P < 0.001, and in AA women and men: 25% vs.17%, P < 0.01. The three variables that most often led to the diagnosis of MetSyn in WA and AA were: low HDL-C, central obesity and hypertension. Less than 40% of AA and less than 25% of WA with the MetSyn had hypertriglyceridemia. Conclusions: Elevated triglyceride levels were uncommon in both WA and AA with MetSyn. As the relative absence of hypertriglyceridemia is associated with a lack of efficacy of MetSyn in AA, caution is warranted in diagnosing MetSyn in WA, the ancestral population of AA. Prospective studies are necessary to determine if an ethnic-specific reformulation of the MetSyn scoring system for lipids might optimize risk identification in black populations.Item Research capacity. Enabling the genomic revolution in Africa(Science, 2014-06) Rotimi, C.; Abayomi, A.; Abimiku, A.; Adabayeri, V.M.; Adebamowo, C.; Adebiyi, E.; Ademola, A.D.; Adeyemo, A.; Adu, D.; Affolabi, D.; Akarolo-Anthony, S.; Akpalu, A.; Ameni, G.; Donkor, P.; Ghansah, A.Our understanding of genome biology, genomics, and disease, and even hu-man history, has advanced tremen-dously with the completion of the Human Genome Project. Technologi-cal advances coupled with significant cost reductions in genomic research have yielded novel insights into disease etiol-ogy, diagnosis, and therapy for some of the world's most intractable and devastat-ing diseases—including ma-laria, HIV/AIDS, tuberculosis, cancer, and diabetes. Yet, de-spite the burden of infectious diseases and, more recently, noncommunicable diseases (NCDs) in Africa, Africans have only par-ticipated minimally in genomics research. Of the thousands of genome-wide association studies (GWASs) that have been conducted globally, only seven (for HIV susceptibility, malaria, tuberculosis, and podoconiosis) have been conducted exclusively on Afri-can participants; four others (for prostate cancer, obsessive compulsive disorder, and anthropometry) included some African participants (www.genome.gov/gwastudies/). As discussed in 2011 (www.h3africa.org), if the dearth of genomics research involving Africans persists, the potential health and economic benefits emanating from genomic science may elude an entire continent. The lack of large-scale genomics studies in Africa is the result of many deep-seated issues, including a shortage of African scien-tists with genomic research expertise, lack of biomedical research infrastructure, lim-ited computational expertise and resources, lack of adequate support for biomedical research by African governments, and the participation of many African scientists in collaborative research at no more than the level of sample collection. Overcoming these limitations will, in part, depend on African Enabling the genomic revolution in Africa By The H3Africa Consortium * H3Africa is developing capacity for health-related genomics research in Africa Yet, roughly a decade ago, newly pro-posed DNA-based taxonomy (11) promised to solve the species debate. A Barcode of Life Data Systems (BOLD) (12) quickly emerged, seeking to provide a reliable, cost-effective solution to the problem of species identification (12) and a standard screening threshold of sequence differ-ence (10× average intraspecific difference) to speed the discovery of new animal spe-cies (13). Sometimes considered a "carica-ture of real taxonomy" (14), this approach failed to identify, perhaps not surprisingly, two American crow species and a number of members of the herring gull Larus ar-gentatus species assemblage above the set threshold (13). Furthermore, despite past (3) and present (6) sequencing projects, carrion crows and hooded crows can also not be differentiated from one another by means of DNA-barcode approaches. By contrast, Poelstra et al. show that much more DNA sequencing data are needed, combined with RNA expression data, to reconstruct the evolution of a reproductive barrier that culminated in the speciation of these two crow taxa. Armed with this new very detailed genetic informa-tion, it is clear that none of the currently formulated species concepts fully apply to these two crow taxa (unless one is willing relax some stringency in the various definitions). In-deed, the genomes of German carrion crows are much more similar to those of hooded crows than to Spanish car-rion crows. Put simply, apart from the few carrion crow type "speciation islands," German carrion crows could be con-sidered to represent hooded crows with a black (carrion crow) phenotype. There is a clear need for ad-ditional population genomic studies using a more dense sampling, especially among the fully black carrion crows, before the complexity of repro-ductive isolation and speciation among these two taxa can be fully understood. The specia-tion genomics strategy already proved itself in unraveling the complexities of mimicry among many Heliconius butterfly taxa (7) and, as in the study of Poelstra et al., stresses the im-portance of using RNA-based information in addition to DNA. Only time will tell if, and when, German carrion crows will adopt the "hooded phenotype," a fate that seems un-avoidable. Until then, we can only applaud these crows for defeating Linnaeus's curse.Item Type 2 diabetes complications and comorbidity in Sub-Saharan Africans(EClinicalMedicine, 2019-10-17) Amoah, A.; Ekoru, K.; Doumatey, A.; Bentley, A.R.; Chen, G.; Zhou, J.; Shriner, D.; Fasanmade, O.; Okafor, G.; Eghan, B.J.; Agyenim-Boateng, K.; Adeleye, J.; Balogun, W.; Acheampong, J.; Johnson, T.; Oli, J.; Adebamowo, C.; Collins, F.; Dunston, G.; Adeyemo, A.; Rotimi, C.Background: Context-specific evidence of the spectrum of type 2 diabetes (T2D) burden is essential for setting priorities and designing interventions to reduce associated morbidity and mortality. However, there are currently limited data on the burden of T2D complications and comorbidity in sub-Saharan Africa (SSA). Methods: T2D complications and comorbidities were assessed in 2,784 participants with diabetes en- rolled from tertiary health centres and contextualised in 3,209 individuals without diabetes in Nigeria, Ghana and Kenya. T2D complications and comorbidities evaluated included cardiometabolic, ocular, neu- rological and renal characteristics. Findings: The most common complications/comorbidities among the T2D participants were hypertension (71%; 95% CI 69–73), hyperlipidaemia (34%; 95% CI 32–36), and obesity (27%; 95% CI 25–29). Additionally, the prevalence of cataracts was 32% (95% CI 30–35), diabetic retinopathy 15% (95% CI 13–17), impaired renal function 13% (95% CI 12–15), and erectile dysfunction (in men) 35% (95% CI 32–38). T2D population- attributable fraction for these comorbidities ranged between 6 and 64%. Interpretation: The burden of diabetes complications and comorbidity is substantial in SSA highlighting the urgent need for innovative public health strategies that prioritise promotion of healthy lifestyles for prevention and early detection of T2D. Also needed are strategies to strengthen health care system ca- pacities to provide treatment and care for diabetes complications.Item Variation in APOL1 contributes to ancestry-level differences in HDLc-kidney function association(International Journal of Nephrology, 2012) Bentley, A.R.; Doumatey, A.P.; Chen, G.; Huang, H.; Zhou, J.; Shriner, D.; Jiang, C.; Zhang, Z.; Liu, G.; Fasanmade, O.; Johnson, T.; Oli, J.; Okafor, G.; Eghan, B.A.; Agyenim-Boateng, K.; Adeleye, J.; Balogun, W.; Adebamowo, C.; Amoah, A.; Acheampong, J.; Adeyemo, A.; Rotimi, C.N.Low levels of high-density cholesterol (HDLc) accompany chronic kidney disease, but the association between HDLc and the estimated glomerular filtration rate (eGFR) in the general population is unclear. We investigated the HDLc-eGFR association in nondiabetic Han Chinese (HC, n = 1100), West Africans (WA, n = 1497), and African Americans (AA, n = 1539). There were significant differences by ancestry: HDLc was positively associated with eGFR in HC (β = 0.13, P 0.0001), but negatively associated among African ancestry populations (WA: -0.19, P 0.0001; AA: -0.09, P = 0.02). These differences were also seen in nationally-representative NHANES data (among European Americans: 0.09, P = 0.005; among African Americans -0.14, P = 0.03). To further explore the findings in African ancestry populations, we investigated the role of an African ancestry-specific nephropathy risk variant, rs73885319, in the gene encoding HDL-associated APOL1. Among AA, an inverse HDLc-eGFR association was observed only with the risk genotype (-0.38 versus 0.001; P = 0.03). This interaction was not seen in WA. In summary, counter to expectation, an inverse HDLc-eGFR association was observed among those of African ancestry. Given the APOL1 × HDLc interaction among AA, genetic factors may contribute to this paradoxical association. Notably, these findings suggest that the unexplained mechanism by which APOL1 affects kidney-disease risk may involve HDLc.Item ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response(nature communications, 2019-06-11) Owusu, S.; Adeyemo, A.A.; Zaghloul, N.A.; Chen, G.; Doumatey, A.P.; Leitch, C.C.; Hostelley, T.L.; Nesmith, J.E.; Zhou, J.; Bentley, A.R.; Shriner, D.; Fasanmade, O.; Okafor, G.; Eghan, B.J.; Agyenim-Boateng, K.; Chandrasekharappa, S.; Adeleye, J.; Balogun, W.; Owusu, S.; Amoah, A.; Acheampong, J.; Johnson, T.; Oli, J.; Adebamowo, C.; Collins, F.; Dunston, G.; Rotimi, C.N.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.