BCX-Africa: Utilizing data science to evaluate the applicability of blood cell traits polygenic risk scores for disease prediction in Africa

Project Summary The goal of the proposed work is to leverage existing genomic data of blood cell traits from the H3Africa and other initiative across Africa for novel gene discovery and genetic risk prediction in Africa ancestry individuals using DSI-Africa funded Open Data Science Platform (ODSP) which allows for effective collaborative research in a resource limited setting. Circulating blood cell traits are critical intermediate clinical phenotypes for a range of disease outcomes including cardiovascular, hematologic and infectious disease. Genetic factors play an important role in determining these traits. However, hundreds of genetic loci have been identified using conventional genome-wide association study (GWAS) approach in European and East Asian-ancestry populations. In view of the genetic diversity of Africans from other ancestries, and their low representation of 1.1% in global GWAS, more studies are required to unravel population specific variants that have been noted to exist in blood cell traits. Given the central importance of Africa to human origins and disease susceptibility, there is a clear scientific and public health need to develop large-scale efforts examining blood cell traits susceptibility in populations of African descent, which might yield insights that will benefit other ethnicities regarding disease etiology and potential therapeutic strategies. Specifically, we will aggregate blood cell traits GWAS data across continental Africa and African Americans leveraging existing partnership in Africa including H3Africa from ~35K individuals. We will test for association between genetic variants and 15 blood cell traits in a meta-analysis GWAS and refine genetic association signals at new and existing blood cell traits association loci. We will develop and assess transferability of Polygenic Risk Score (PRS) for blood cell traits risk in Africa including evaluating the predictivity of the blood cell traits PRS for a range of non-communicable diseases including leukaemia (N=5,926), Hypertension (N = 39,784), Stroke (N=5,540), Diabetes mellitus (N=20,506) and sickle cell disease (N= 5,704) in collaboration with participating non-academic partner on the project (54gene Lagos Nigeria). Our proposal is directly aimed at a key mission of RFA-RM-22-023, to support harnessing data science for health discovery, that will not only generate important findings relevant to human health, but also serve as a vehicle to improve the genomic data science research capacity in Africa. Our proposal also directly addresses the NIH strategic plan for data science. The unique collaboration within the Human Heredity and Health in Africa (H3Africa) for a cross-group analyse in Africa strengthen the capacity of scientific research through scientific training in all participating institution, which facilitate opportunity for shared expertise and resources.