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.
