Linking the plasma proteome to genetics in individuals from continental Africa provides insights into type 2 diabetes pathogenesis

Individuals of African ancestry remain largely underrepresented in genetic and proteomic studies. Here we measure the levels of 2,873 proteins in plasma samples from 163 individuals with type 2 diabetes (T2D) or prediabetes and 362 normoglycemic controls from the Ugandan population. We identify 88 differentially expressed proteins between the two groups. We link genome-wide data to protein expression levels and construct a protein quantitative trait locus (pQTL) map for this population. We identify 399 independent associations with 346 (86.7%) cis-pQTLs and 53 (13.3%) trans-pQTLs; 16.7% of the cis-pQTLs and all of the trans-pQTLs have not been previously reported in individuals of African ancestry. Of these, 37 pQTLs have not been previously reported in any population. We find evidence for colocalization between a pQTL and T2D genetic risk. Our findings reveal proteins causally implicated in the pathogenesis of T2D, which may be leveraged for personalized medicine tailored to individuals of African ancestry.