Linking the plasma proteome to genetics in individuals from continental Africa provides insights into type 2 diabetes pathogenesis
Soremekun, O.; Park, Y.-c.; Tutino, M.; Kalungi, A.; Nyirenda, M. J.; Fatumo, S.; Zeggini, E.
Show abstract
Individuals of African ancestry remain largely underrepresented in genetic and proteomic studies. Here, we measure the levels of 2,873 proteins using the Olink proximity extension assay in plasma samples from 163 individuals with type 2 diabetes (T2D) or prediabetes and 362 normoglycemic controls from the Ugandan population for the first time. We identify 88 differentially expressed proteins between the two groups and 208 proteins associated with cardiometabolic traits. We link genome-wide data to protein expression levels and construct the first protein quantitative trait locus (pQTL) map in 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 African-ancestry individuals. Of these, 37 pQTLs have not been previously reported in any population. We find evidence for colocalization between a pQTL for SIRPA and T2D genetic risk. Mendelian randomization analysis identified 20 proteins causally associated with T2D. Our findings reveal proteins causally implicated in the pathogenesis of T2D, which may be leveraged for personalized medicine tailored to African-ancestry individuals.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Genetic analysis of blood molecular phenotypes reveals regulatory networks affecting complex traits: a DIRECT study 97%
- The impact of non-additive genetic associations on age-related complex diseases. 97%
- A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins 96%
Similar papers in this journal
- Widespread recessive effects on common diseases in a cohort of 44,000 British Pakistanis and Bangladeshis with high autozygosity 96%
- Integration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension 96%
- Characterization of exome variants and their metabolic impact in 6,716 American Indians from Southwest US 96%
Similar papers in this journal
- Pathway-specific polygenic scores substantially increase the discovery of gene-adiposity interactions impacting liver biomarkers 95%
- Polygenic risk score prediction accuracy convergence 94%
- Multivariate adaptive shrinkage improves cross-population transcriptome prediction for transcriptome-wide association studies in underrepresented populations 94%
Similar papers in this journal
- Genetic associations with ratios between protein levels detect new pQTLs and reveal protein-protein interactions 96%
- Proteome-wide Mendelian randomization in global biobank meta-analysis reveals multi-ancestry drug targets for common diseases 95%
- Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines 95%
Similar papers in this journal
- Whole Genome Sequence Association Analysis of Fasting Glucose and Fasting Insulin Levels in Diverse Cohorts from the NHLBI TOPMed Program 97%
- Composite trait Mendelian Randomization reveals distinct metabolic and lifestyle consequences of differences in body shape 94%
- Genome-wide meta-analysis of iron status biomarkers and the effect of iron on all-cause mortality in HUNT 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.