Stroke genomics in people of African ancestry: charting new paths: review article

Akinyemi, Rufus; Ovbiagele, Bruce; Akpalu, Albert; Jenkins, Carolyn; Sagoe, Kwamena W.; Owolabi, Lukman; Sarfo, Fred Stephen; Obiako, Reginald; Gebreziabher, M; Melikam, E; Warth, Stephanie; Arulogun, Oyedunni; Lackland, Daniel T.; Ogunniyi, Adesola; Tiwari, Hemant K.; Kalaria, Raj N.; Arnett, Donna K.; Owolabi, Mayowa

doi:10.5830/cvja-2015-039

Cited by 27 publications

(32 citation statements)

References 116 publications

(136 reference statements)

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“…5, 18–23 Although some of these loci have been associated with specific subtypes, genetic overlaps have also been reported among them. 20, 22 For example, large artery atherosclerosis and small vessel disease, which were previously treated as genetically distinct, may share a substantial genetic component.…”

Section: Discussionmentioning

confidence: 99%

“…25 Promising candidates for risk alleles in ICH identified in populations (which had no continental Africans), include variants of the genes Apolipoprotein E ( APOE ), ACE, PMF1/SLC25A44 , COL4A2 , and MTHFR 18, 23, 26 . Other genetic variants related to hemostasis, lipid metabolism, inflammation, and the central nervous system microenvironment as well as the locus 1q22 25 have also been linked to ICH in single candidate gene studies.…”

Section: Discussionmentioning

confidence: 99%

“…This is because novel variants (SNPs/copy number variants CNVs/insertion-deletions InDels) that contribute to the higher burden, earlier age of onset and poorer outcomes of stroke in people of African ancestry are yet to be characterized. 2, 5, 18 …”

Section: Discussionmentioning

confidence: 99%

“…5, 18, 32, 33, 36 These haplotypes are common in African ancestry populations but absent in European Caucasians and Asians, presumably due to evolutionary positive selection because these APOL1 variants confer resistance to lethal Trypanosoma brucei infections, which cause African sleeping sickness. 5, 18, 32, 33 Only by studying people of African ancestry, were the associations of the G1 and G2 APOL1 variants identified, and these variants turned out to account for the large amount of the ethnic disparity in end-stage renal disease that had long been recognized between African and European ancestry populations. 5, 18, 32, 33 …”

Section: Discussionmentioning

confidence: 99%

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Advancing stroke genomic research in the age of Trans-Omics big data science: Emerging priorities and opportunities

Owolabi

Peprah

et al. 2017

Journal of the Neurological Sciences

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Background We systematically reviewed the genetic variants associated with stroke in genome-wide association studies (GWAS) and examined the emerging priorities and opportunities for rapidly advancing stroke research in the era of Trans-Omics science. Methods Using the PRISMA guideline, we searched PubMed and NHGRI- EBI GWAS catalog for stroke studies from 2007 till May 2017. Results We included 31 studies. The major challenge is that the few validated variants could not account for the full genetic risk of stroke and have not been translated for clinical use. None of the studies included continental Africans. Genomic study of stroke among Africans presents a unique opportunity for the discovery, validation, functional annotation, trans-omics study and translation of genomic determinants of stroke with implications for global populations. This is because all humans originated from Africa, a continent with a unique genomic architecture and a distinctive epidemiology of stroke; as well as substantially higher heritability and resolution of fine mapping of stroke genes. Conclusion Understanding the genomic determinants of stroke and the corresponding molecular mechanisms will revolutionize the development of a new set of precise biomarkers for stroke prediction, diagnosis and prognostic estimates as well as personalized interventions for reducing the global burden of stroke.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Advancing stroke genomic research in the age of Trans-Omics big data science: Emerging priorities and opportunities

Owolabi

Peprah

et al. 2017

Journal of the Neurological Sciences

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“…Combined large accurate datasets from diverse settings are required to fully understand the genomic and environmental underpinnings of stroke and its discrete subtypes as well as the relationship between stroke neuroimaging phenotype and its clinical manifestations, prognosis and outcome (6;7). Such multicenter research involving multiple investigators and large datasets require secure archiving, as well as accurate and reproducible standard classification formats.…”

Section: Introductionmentioning

confidence: 99%

Development and Reliability of a User-Friendly Multicenter Phenotyping Application for Hemorrhagic and Ischemic Stroke

Owolabi

Ogbole

Akinyemi

et al. 2017

Journal of Stroke and Cerebrovascular Diseases

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Background AIM on ClearCanvas Enriched Stroke- phenotyping Software (ACCESS) is a novel standalone computer software application that allows creation of simple standardized annotations for reporting brain images of all stroke types. We developed the ACCESS application and determined its inter-rater and intra-rater reliability in the Stroke Investigative Research and Educational Network (SIREN) study to assess its suitability for multicenter studies. Methods One hundred randomly selected stroke imaging reports from five SIREN sites were reevaluated by four trained independent raters to determine inter-rater reliability of ACCESS (version 12.0) software for stroke phenotyping. To determine intra-rater reliability, six raters reviewed the same cases previously reported by them after a month interval. Ischemic stroke was classified using the Oxfordshire Community Stroke Project (OCSP), TOAST and ASCO protocols, while hemorrhagic stroke was classified using the SMASH-U protocol in ACCESS. Agreement among raters was measured with Cohen’s kappa statistics. Results For primary stroke type, inter-rater agreement was 0.98 (95%CI: 0.94–1.00) while intra-rater agreement was 1.00 (95%CI: 1.00). For OCSP subtypes, inter-rater agreement was 0.97 (95%CI: 0.92–1.00) for the Partial Anterior Circulation Infarcts (PACI), 0.92 (95%CI: 0.76–1.00) for the Total Anterior Circulation Infarcts(TACI) and excellent for both Lacunar Infarct (LACI) and Posterior Circulation Infarcts (POCI). Intra-rater agreement was 0.97 (0.90–1.00) while inter-rater agreement was 0.93 (95%CI: 0.84–1.00) for TOAST subtypes. Inter-rater agreement ranged between 0.78 (cardioembolic) to 0.91 (large artery atherosclerotic) for ASCO subtypes and was 0.80 (95%CI: 0.56–1.00) for SMASH-U subtypes. Conclusion The ACCESS application facilitates concordant and reproducible classification of stroke subtypes by multiple investigators, making it suitable for clinical and multicenter research.

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Evolutionary history of disease‐susceptibility loci identified in longitudinal exome‐wide association studies

Yasukochi

Sakuma

Takeuchi

et al. 2019

Molec Gen & Gen Med

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Background Our longitudinal exome‐wide association studies previously detected various genetic determinants of complex disorders using ~26,000 single‐nucleotide polymorphisms (SNPs) that passed quality control and longitudinal medical examination data (mean follow‐up period, 5 years) in 4884–6022 Japanese subjects. We found that allele frequencies of several identified SNPs were remarkably different among four ethnic groups. Elucidating the evolutionary history of disease‐susceptibility loci may help us uncover the pathogenesis of the related complex disorders. Methods In the present study, we conducted evolutionary analyses such as extended haplotype homozygosity, focusing on genomic regions containing disease‐susceptibility loci and based on genotyping data of our previous studies and datasets from the 1000 Genomes Project. Results Our evolutionary analyses suggest that derived alleles of rs78338345 of GGA3, rs7656604 at 4q13.3, rs34902660 of SLC17A3, and six SNPs closely located at 12q24.1 associated with type 2 diabetes mellitus, obesity, dyslipidemia, and three complex disorders (hypertension, hyperuricemia, and dyslipidemia), respectively, rapidly expanded after the human dispersion from Africa (Out‐of‐Africa). Allele frequencies of GGA3 and six SNPs at 12q24.1 appeared to have remarkably changed in East Asians, whereas the derived alleles of rs34902660 of SLC17A3 and rs7656604 at 4q13.3 might have spread across Japanese and non‐Africans, respectively, although we cannot completely exclude the possibility that allele frequencies of disease‐associated loci may be affected by demographic events. Conclusion Our findings indicate that derived allele frequencies of nine disease‐associated SNPs (rs78338345 of GGA3, rs7656604 at 4q13.3, rs34902660 of SLC17A3, and six SNPs at 12q24.1) identified in the longitudinal exome‐wide association studies largely increased in non‐Africans after Out‐of‐Africa.

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Stroke genomics in people of African ancestry: charting new paths: review article

Cited by 27 publications

References 116 publications

Advancing stroke genomic research in the age of Trans-Omics big data science: Emerging priorities and opportunities

Advancing stroke genomic research in the age of Trans-Omics big data science: Emerging priorities and opportunities

Development and Reliability of a User-Friendly Multicenter Phenotyping Application for Hemorrhagic and Ischemic Stroke

Evolutionary history of disease‐susceptibility loci identified in longitudinal exome‐wide association studies

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