Polygenic risk scores for CARDINAL study

Adebamowo, Clement; Adeyemo, Adebowale; Ashaye, Adeyinka; Akpa, Onoja Matthew; Chikowore, Tinashe; Choudhury, Ananyo; Fakim, Yasmina Jaufeerally; Fatumo, Segun; Hanchard, Neil A.; Hauser, Michael A.; Mitchell, Braxton D.; Mulder, Nicola; Ofori-Acquah, Solomon Fiifi; Owolabi, Mayowa; Ramsay, Michèle; Tayo, Bamidele O.; VasanthKumar, Archana Bhavani; Zhang, Yuji; Adebamowo, Clement

doi:10.1038/s41588-022-01074-3

Cited by 7 publications

(4 citation statements)

References 25 publications

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“…More dynamic methods to estimate the effects of specific genetic variations given the genetic, demographic, and clinical risk factor backgrounds of the individual are anticipated to be developed as representation from Africa and other underrepresented populations increases. It is reassuring to see a coordinated efforts such as the Polygenic RIsk MEthods in Diverse Populations (PRIMED) that promises to deliver new methods for risk prediction in diverse ancestry and specifically a pan-Africa initiative—CARdiometabolic Disorders IN African-ancestry PopuLations (CARDINAL) project which aim to test PRS performance on African individuals with phenotype and genotype data available from H3Africa projects [ 70 ].…”

Section: Factors Contributing To Poor Transferability Of Prs In Afric...mentioning

confidence: 99%

Polygenic risk scores for disease risk prediction in Africa: current challenges and future directions

Fatumo,

Sathan,

Samtal

et al. 2023

Genome Med

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Early identification of genetic risk factors for complex diseases can enable timely interventions and prevent serious outcomes, including mortality. While the genetics underlying many Mendelian diseases have been elucidated, it is harder to predict risk for complex diseases arising from the combined effects of many genetic variants with smaller individual effects on disease aetiology. Polygenic risk scores (PRS), which combine multiple contributing variants to predict disease risk, have the potential to influence the implementation for precision medicine. However, the majority of existing PRS were developed from European data with limited transferability to African populations. Notably, African populations have diverse genetic backgrounds, and a genomic architecture with smaller haplotype blocks compared to European genomes. Subsequently, growing evidence shows that using large-scale African ancestry cohorts as discovery for PRS development may generate more generalizable findings. Here, we (1) discuss the factors contributing to the poor transferability of PRS in African populations, (2) showcase the novel Africa genomic datasets for PRS development, (3) explore the potential clinical utility of PRS in African populations, and (4) provide insight into the future of PRS in Africa.

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Section: Factors Contributing To Poor Transferability Of Prs In Afric...mentioning

confidence: 99%

Polygenic risk scores for disease risk prediction in Africa: current challenges and future directions

Fatumo,

Sathan,

Samtal

et al. 2023

Genome Med

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“…An initiative created in response to the changing distribution of communicable diseases and the rising burden of noncommunicable diseases, as well as the recognition that low-and middle-income countries (LMICs), including those in Sub-Saharan Africa, will need to expand their health-care capacities to effectively respond to these epidemiological transitions. CARDINAL (Adebamowo, C.A. et al, 2022) aims to integrate phenotype and genomic datasets from 50,000 African individuals from seven cohort studies and evaluate PRSs to develop a novel method that considers ancestry-specific genomic regions to improve PRS prediction in populations with genetic substructure.…”

Section: Contribution To Collaborative Studiesmentioning

confidence: 99%

“…We are part of the CARDINAL (CARDiometabolic Disorders IN African-ancestry PopuLations) which is study site of an NIH-funded Polygenic Risk Methods in Diverse Populations (PRIMED) Consortium https://primedconsortium.org/. CARDINAL (Adebamowo, C.A. et al ., 2022) aims to integrate phenotype and genomic datasets from 50,000 African individuals from seven cohort studies and evaluate PRSs to develop a novel method that considers ancestry-specific genomic regions to improve PRS prediction in populations with genetic substructure.…”

Section: Introductionmentioning

confidence: 99%

Uganda Genome Resource: A rich research database for genomic studies of communicable and non-communicable diseases in Africa

Fatumo

Mugisha

Soremekun

et al. 2022

Preprint

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The Uganda Genome Resource (UGR) is a well characterised genomic database, with a range of phenotypic communicable and non-communicable diseases and risk factors generated from the Uganda General Population Cohort (GPC) - a population-based open cohort study established in 1989 by the Medical Research Council (MRC) UK in collaboration with the Uganda Virus Research Institute (UVRI).In 2011, UGR was launched with genotype data on ∼5000 and whole genome sequence data on ∼2000 Ugandan individuals from 9 ethno-linguistic groups. Leveraging other available platforms at the MRC Uganda such as Biorepository centre for sample storage, Clinical Diagnostic Laboratory Service (CDLS) for sample diagnostic testing, sequencing platform for DNA extraction, Uganda Medical informatics Unit (UMIC) for large-scale data analysis, GPC for additional sample collection, UGR is strategically poised to expand and generate scientific discoveries.Here, we describe UGR and highlight the important genetic findings thus far including how UGR is providing opportunities to: (1) discover novel disease susceptibility genetic loci; (2) refine association signals at new and existing loci; (3) develop and test Polygenic Risk Score (PRS) to determine individual’s disease risk; 4) assess how some risk factors including infectious diseases are causally related to non-communicable diseases (NCDs) in Africa; (5) develop research capacity for genomics in Africa; and (6) enhance African participation in the global genomics research arena. Leveraging established research infrastructure, expertise, local genomic leadership, global collaboration and strategic funding, we anticipate that UGR can develop further to a comparable level of European and Asian large-scale genomic initiatives.

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“…We suggest that for PRS to be applied at scale, several important developments are needed to be advanced: (a) to further the collection of diverse data through biobanks, (b) the development of clinical trials making use of PRS and (c) the generation of public/private partnerships with commercial genetic testing companies. For this, the research community will need to use and develop new bioinformatics methods and machine learning approaches in order to analyse and generate PRS data [ 15 ]. PRS will need to be integrated with electronic health records to provide clinicians with information about an individual’s health risks.…”

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confidence: 99%

Generalisation of genomic findings and applications of polygenic risk scores

Corpas

Fatumo

2023

BMC Med Genomics

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Polygenic Risk Scores (PRS) (also known as polygenic scores, genetic risk scores or polygenic indexes) capture genetic contributions of a multitude of markers that characterise complex traits. Although their likely application to precision medicine remains to be established, promising advances have included their ability to stratify high risk individuals and targeted screening interventions. Current PRS have been mostly optimised for individuals of Northern European ancestries. If PRS are to become widespread as a tool for healthcare applications, more diverse populations and greater capacity for derived interventions need to be accomplished. In this editorial we aim to attract submissions from the research community that highlight current challenges in development of PRS applications at scale. We also welcome manuscripts that delve into the ethical, social and legal implications that the implementation of PRS may generate.

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Polygenic risk scores for CARDINAL study

Cited by 7 publications

References 25 publications

Polygenic risk scores for disease risk prediction in Africa: current challenges and future directions

Polygenic risk scores for disease risk prediction in Africa: current challenges and future directions

Uganda Genome Resource: A rich research database for genomic studies of communicable and non-communicable diseases in Africa

Generalisation of genomic findings and applications of polygenic risk scores

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