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

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.

Developing Clinical Phenotype Data Collection Standards for Research in Africa.

Modern biomedical research is characterised by its high-throughput and interdisciplinary nature. Multiproject and consortium-based collaborations requiring meaningful analysis of multiple heterogeneous phenotypic datasets have become the norm; however, such analysis remains a challenge in many regions across the world. An increasing number of data harmonisation efforts are being undertaken by multistudy collaborations through either prospective standardised phenotype data collection or retrospective phenotype harmonisation. In this regard, the Phenotype Harmonisation Working Group (PHWG) of the Human Heredity and Health in Africa (H3Africa) consortium aimed to facilitate phenotype standardisation by both promoting the use of existing data collection standards (hosted by PhenX), adapting existing data collection standards for appropriate use in low- and middle-income regions such as Africa, and developing novel data collection standards where relevant gaps were identified. Ultimately, the PHWG produced 11 data collection kits, consisting of 82 protocols, 38 of which were existing protocols, 17 were adapted, and 27 were novel protocols. The data collection kits will facilitate phenotype standardisation and harmonisation not only in Africa but also across the larger research community. In addition, the PHWG aims to feed back adapted and novel protocols to existing reference platforms such as PhenX.