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

Nat Genet. 2026 Jan;58(1):39-46. doi: 10.1038/s41588-025-02421-w. Epub 2026 Jan 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Black People* / genetics
  • Blood Proteins* / genetics
  • Case-Control Studies
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prediabetic State / blood
  • Prediabetic State / genetics
  • Proteome* / genetics
  • Proteomics
  • Quantitative Trait Loci* / genetics
  • Uganda

Substances

  • Proteome
  • Blood Proteins