Whole-genome Studies of Malagasy People Uncover Novel Body Composition Associations

Summary The majority of human genomic research studies have been conducted in European ancestry cohorts, at the loss of detecting potentially novel and globally impactful findings. Here, we present the first whole genome sequence data and genome-wide association study in a cohort of 264 Malagasy individuals from three locations on the island of Madagascar. We describe genetic variation in this Malagasy cohort, providing insight into the shared and unique patterns of genetic variation across the island. We observe phenotypic variation by location, and find high rates of hypertension particularly in the Southern Highlands as well as elevated malaria prevalence in the West Coast relative to other sites. We find a number of genetic associations with body composition traits, including many variants that are unique to African populations or populations with admixed African ancestry such as Madagascar. This study highlights the utility of including diverse populations in genomic research for the potential to gain novel insights, even with small cohort sizes. This project was conducted in partnership and consultation with local Malagasy stakeholders and serves as an example for equitable genomic research with potential impacts on our understanding of human health and disease.