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Linking the plasma proteome to genetics in individuals from continental Africa provides insights into type 2 diabetes pathogenesis.
Nat. Genet. 58, 39–46 (2026)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Angiogenesis; Associations; Metaanalysis; Discovery; Diagnosis; Hba1c; Risk
ISSN (print) / ISBN
1061-4036
e-ISSN
1546-1718
Journal
Nature Genetics
Quellenangaben
Volume: 58,
Pages: 39–46
Publisher
Nature Publishing Group
Publishing Place
New York, NY
Reviewing status
Peer reviewed
Institute(s)
Institute of Translational Genomics (ITG)
Grants
Helmholtz Zentrum Mnchen - Deutsches Forschungszentrum fr Gesundheit und Umwelt (GmbH)