Year: 2021
Type: preprint
Abstract: Objective Polygenic prediction of type 2 diabetes in continental Africans is adversely affected by the limited number of genome-wide association studies (GWAS) of type 2 diabetes from Africa, and the poor transferability of European derived polygenic risk scores (PRS) in diverse ethnicities. We set out to evaluate if African American or multi-ethnic 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 type 2 diabetes GWAS of the Million Veteran Program (MVP) study. The South African Zulu study (1602 cases and 976 controls) was used as the target data set. Replication and assessment of the best predictive PRS association with age at diagnosis was done in the Africa America Diabetes Mellitus (AADM) study (1031 cases and 738 controls). Results The African American derived PRS was more predictive of type 2 diabetes compared to the European and multi-ethnic derived scores. Notably, participants in the 10 th decile of this PRS had a 3.19-fold greater risk (OR 3.19; 95%CI (1.94-5.29), p = 5.33 x10 -6 ) of developing diabetes and were diagnosed 2.6 years earlier compared to those in the first decile. Conclusions African American derived PRS enhances polygenic prediction of type 2 diabetes in continental Africans. Improved representation of non-Europeans populations (including Africans) in GWAS, promises to provide better tools for precision medicine interventions in type 2 diabetes.
Institutions: University of the Witwatersrand, National Institutes of Health, Philadelphia VA Medical Center, St George's, University of London, Imperial College London, University of KwaZulu-Natal, Centre for Human Genetics, University of Oxford, London School of Hygiene & Tropical Medicine, MRC/UVRI & LSHTM Uganda Research Unit, Uganda Virus Research Institute
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: London School of Hygiene and Tropical Medicine, Wellcome Trust, National Institute for Health and Care Research, British Heart Foundation, Imperial College London, New Partnership for Africa's Development, Servier, Victor Daitz Foundation, National Institutes of Health, Medical Research Council, St. George's, University of London, Alliance for Accelerating Excellence in Science in Africa, National Institute of Mental Health, National Human Genome Research Institute, NIH Office of the Director, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases, Center for Information Technology
Awards: G1358062850, Makerere University UVRI Centre of Excellence for Infection & Immunity Research and Training (MUII-plus), Research Excellence (round 3), Characterisation of gene-lifestyle interactions associated with obesity-related traits in African populations, MINORITY INTERNATIONAL RESEARCH TRAINING GRANT, G1801186217, G2041748056, G2190046927, G2697783883, G3442742860, G5264857295, Assessing the impact of genetic variation on chronic kidney disease in Africa, Transgenerational Epigenomics of Trauma and PTSD in Rwanda, G5974598883, G6114135618, Assessing the impact of genetic variation on chronic kidney disease in Africa, Characterisation of gene-lifestyle interactions associated with obesity- related traits in African populations, G7227888905, G7279930290, G780909024, G8039954816, G8592617908, G9000159767
OpenAlex ID: W3129904616