Polygenic Prediction of Type 2 Diabetes in Africa.

Autor:	Chikowore T; MRC/Wits Developmental Pathways for Health Research Unit, Department of Pediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Ekoru K; Center for Research on Genomics and Global Health, National Institute of Health, Bethesda, MD., Vujkovi M; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA., Gill D; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, U.K.; Clinical Pharmacology and Therapeutics Section, Institute of Medical and Biomedical Education and Institute for Infection and Immunity, St George's, University of London, London, U.K., Pirie F; Department of Diabetes and Endocrinology, University of KwaZulu-Natal, Durban, South Africa., Young E; Omnigen Biodata Ltd, Cambridge, U.K., Sandhu MS; Department of Epidemiology and Biostatistics, Imperial College, London, U.K., McCarthy M; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K., Rotimi C; Center for Research on Genomics and Global Health, National Institute of Health, Bethesda, MD., Adeyemo A; Center for Research on Genomics and Global Health, National Institute of Health, Bethesda, MD., Motala A; Department of Diabetes and Endocrinology, University of KwaZulu-Natal, Durban, South Africa., Fatumo S; London School of Hygiene and Tropical Medicine, London, U.K.; The African Computational Genomics Research Group, MRC/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine (Uganda Research Unit), Entebbe, Uganda.
Jazyk:	angličtina
Zdroj:	Diabetes care [Diabetes Care] 2022 Mar 01; Vol. 45 (3), pp. 717-723.
DOI:	10.2337/dc21-0365
Abstrakt:	Objective: Polygenic prediction of type 2 diabetes (T2D) in continental Africans is adversely affected by the limited number of genome-wide association studies (GWAS) of T2D from Africa and the poor transferability of European-derived polygenic risk scores (PRSs) in diverse ethnicities. We set out to evaluate if African American, European, or multiethnic-derived PRSs would improve polygenic prediction in continental Africans. Research Design and Methods: Using the PRSice software, ethnic-specific PRSs were computed with weights from the T2D GWAS multiancestry meta-analysis of 228,499 case and 1,178,783 control subjects. The South African Zulu study (n = 1,602 case and 981 control subjects) was used as the target data set. Validation and assessment of the best predictive PRS association with age at diagnosis were conducted in the Africa America Diabetes Mellitus (AADM) study (n = 2,148 case and 2,161 control subjects). Results: The discriminatory ability of the African American and multiethnic PRSs was similar. However, the African American-derived PRS was more transferable in all the countries represented in the AADM cohort and predictive of T2D in the country combined analysis compared with the European and multiethnic-derived scores. Notably, participants in the 10th decile of this PRS had a 3.63-fold greater risk (odds ratio 3.63; 95% CI 2.19-4.03; P = 2.79 × 10-17) per risk allele of developing diabetes and were diagnosed 2.6 years earlier than those in the first decile. Conclusions: African American-derived PRS enhances polygenic prediction of T2D in continental Africans. Improved representation of non-European populations (including Africans) in GWAS promises to provide better tools for precision medicine interventions in T2D. (© 2022 by the American Diabetes Association.)
Databáze:	MEDLINE
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