Nyambo, Thomas B.2023-09-142023-09-142022-06-01Hui, D., Harris, D., Mcquillan, M., Hansen, M., Ranciaro, A., Beggs, W., Mpoloka, S.W., Woldemeskel, D., Njamnshi, A.K., Nyambo, T.B. and Chanock, S., 2022. 1284-P: Genetic and Lifestyle Associations with Cardiometabolic Traits and Diabetes Risk Factors in Ethnically Diverse Africans. Diabetes, 71(1).https://doi.org/10.2337/db22-1284-Phttp://hdl.handle.net/123456789/1177African ancestry populations are underrepresented in human genetic studies, which leaves a knowledge gap about genetic and environmental risk factors for metabolic disease which can bias healthcare treatment. To alleviate these shortcomings, we conducted a series of genome-wide association studies of cardiometabolic traits in a diverse sampling of ∼2,500 (max sample size) ethnically and geographically diverse Africans from populations practicing agriculturalist, hunter-gatherer, and pastoralist subsistence strategies. This study includes the Fulani pastoralists who have a relatively high incidence of adult-onset diabetes, despite having a low average body mass index (BMI) . All individuals in the present study are sampled from rural populations that have relatively homogeneous lifestyles and diet within a community. This unique aspect to the study cohort allows for within- and between- group comparisons to identify trait variation attributable to genetics vs. lifestyle variation. Subjects were genotyped on a new African-focused SNP array from the Human Heredity and Health in Africa (H3 Africa) consortium. Genome-wide data was imputed based on a panel of African whole-genome sequences and data from the 1000 genomes project, resulting in a total of million variants for trait association analysis. Genetic associations were tested for BMI, blood pressure, and blood biomarkers of cardiometabolic health. We checked for replication of genotype/phenotype associations by comparison to large non-African cohorts studied for the same traits. We find that most associations identified in non-African populations do not replicate in the Africans. However, we identified a number of novel loci associated with cardiometabolic traits in the African populations. This study has important implications for identifying genetic risk factors that may play a role in metabolic disease in individuals of African ancestry.enLifestyleEthnically Diverse AfricansGeneticsArticle