Pharmacogenomic implications of the evolutionary history of infectious diseases in Africa

Baker, Jennifer L.; Shriner, Daniel; Bentley, Amy R.; Rotimi, Charles N.

doi:10.1038/tpj.2016.78

Cited by 22 publications

(24 citation statements)

References 191 publications

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“…PAGE allele frequencies can therefore aid in expanding the reach of precision medicine to encompass individuals of diverse ancestry, particularly when combined with other studies. 47,48 . However, as previously described, if differential LD patterns are found in different populations then the utility of the rs2395029 tag SNP as a screen may not be universal in all populations.…”

Section: Relevance Of Multi-ethnic Genetic Variation To Clinical Carementioning

confidence: 99%

The PAGE Study: How Genetic Diversity Improves Our Understanding of the Architecture of Complex Traits

Graff

et al. 2017

Preprint

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Summary/AbstractGenome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development, and clinical guidelines. However, the dominance of European-ancestry populations in GWAS creates a biased view of the role of human variation in disease, and hinders the equitable translation of genetic associations into clinical and public health applications. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioral phenotypes in 49,839 non-European individuals. Using strategies designed for analysis of multi-ethnic and admixed populations, we confirm 574 GWAS catalog variants across these traits, and find 38 secondary signals in known loci and 27 novel loci. Our data shows strong evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts, and insights into clinical implications. We strongly advocate for continued, large genome-wide efforts in diverse populations to reduce health disparities.

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Section: Relevance Of Multi-ethnic Genetic Variation To Clinical Carementioning

confidence: 99%

The PAGE Study: How Genetic Diversity Improves Our Understanding of the Architecture of Complex Traits

Graff

et al. 2017

Preprint

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“…This result illustrates how ancestry-specific findings may be transferable to other groups that share components of genetic ancestry-in this case, the African ancestry present in both African Americans and some Hispanic/Latinos. The PAGE study can therefore aid in expanding the reach of precision medicine to encompass individuals of diverse ancestry, particularly when combined with other studies 31,32 .…”

mentioning

confidence: 99%

Genetic analyses of diverse populations improves discovery for complex traits

Wojcik

Graff

Nishimura

et al. 2019

Nature

780

722

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Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry 1-3. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific 4-10. Additionally, effect sizes and their derived risk prediction scores derived in one population may Reprints and permissions information is available at http://www.nature.com/reprints.

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“…The SIREN investigators involved in the largest study on stroke in Africa to date, were the first to demonstrate an association between APOL1 variant rs73885319 and small vessel disease (lacunar) strokes among West Africans [39]. Among African Americans, the APOL1 gene has been propounded as a risk locus for chronic kidney disease [54] and West Africans, among whom small vessel disease strokes are the commonest stroke phenotype, have the highest frequencies of APOL1-associated kidney variants on the globe with the Akans of Ghana [55] reporting 43.6% and that among the Yorubas of Nigeria [37,38] being 34.2%. However, it is worth emphasizing the conflicting reports of associations between APOL1 renal related variants and occurrence of strokes from large prospective studies.…”

Section: Discussionmentioning

confidence: 99%

Estimated glomerular filtration rate predicts incident stroke among Ghanaians with diabetes and hypertension

Mobula

Sarfo‐Kantanka

Adamu

et al. 2019

Journal of the Neurological Sciences

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Background: Sub-Saharan Africa is currently experiencing a high burden of both chronic kidney disease (CKD) and stroke as a result of a rapid rise in shared common vascular risk factors such as hypertension and diabetes mellitus. However, no previous study has prospectively explored independent associations between CKD and incident stroke occurrence among indigenous Africans. This study sought to fill this knowledge gap. Methods: A prospective cohort study involving Ghanaians adults with hypertension or type II diabetes mellitus from 5 public hospitals. Patients were followed every 2 months in clinic for 18 months and assessed clinically for first ever stroke by physicians. Serum creatinine derived estimated glomerular filtration rates (eGFR) were determined at baseline for 2631 (81.7%) out of 3296 participants. We assessed associations between eGFR and incident stroke using a multivariate Cox Proportional Hazards regression model. Results: Stroke incidence rates (95% CI) increased with decreasing eGFR categories of 89, 60-88, 30-59 and < 29 ml/min corresponding to incidence rates of 7.58 (3.58-13.51), 14.45 (9.07-21.92), 29.43 (15.95-50.04) and 66.23 (16.85-180.20)/1000 person-years respectively. Adjusted hazard ratios (95%CI) for stroke occurrence according to eGFR were 1.42 (0.63-3.21) for eGFR of 60-89 ml/min, 1.88 (1.17-3.02) for 30-59 ml/min and 1.52 (0.93-2.43) for < 30 ml/min compared with eGFR of > 89 ml/min. Adjusted HR for stroke occurrence among patients with hypertension with eGFR < 60 ml/min was 3.69 (1.49-9.13), p = .0047 and among those with diabetes was 1.50 (0.56-3.98), p = .42. Conclusion: CKD is dose-dependently associated with occurrence of incident strokes among Ghanaians with hypertension and diabetes mellitus. Further studies are warranted to explore interventions that could attenuate the risk of stroke attributable to renal disease among patients with hypertension in SSA.

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Pharmacogenomic implications of the evolutionary history of infectious diseases in Africa

Cited by 22 publications

References 191 publications

The PAGE Study: How Genetic Diversity Improves Our Understanding of the Architecture of Complex Traits

The PAGE Study: How Genetic Diversity Improves Our Understanding of the Architecture of Complex Traits

Genetic analyses of diverse populations improves discovery for complex traits

Estimated glomerular filtration rate predicts incident stroke among Ghanaians with diabetes and hypertension

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