Distinct Genetic Determinants of Plasma Inflammatory Proteins in Tanzanian and Dutch Populations

Abstract Understanding the genetic regulation of plasma inflammatory proteins is essential for bridging the gap between genetics and disease biology. While studies in European populations have highlighted significant genetic influences on inflammatory protein levels, African populations remain underrepresented in immunogenetic research. Here, we compare the genetic determinants of 72 inflammatory proteins quantified using the Olink Target 96 Inflammation panel in two cohorts from the Human Functional Genomics Project. The study included 286 healthy Tanzanians (146 males and 140 females) and 340 Dutch participants (175 males and 165 females). Genotyping was conducted using the Illumina Global Screening Array (GSA) for the Tanzanian cohort and the HumanOmniExpressExome-8 for the Dutch cohort. Our genome-wide protein quantitative trait locus (pQTL) analysis identified 10 genome-wide significant FDR-corrected pQTLs in each population, including a missense variant affecting cluster of differentiation 6 (CD6) concentrations, which is implicated in multiple autoimmune and inflammatory diseases. We identified three trans- and seven cis-pQTLs in the Tanzanian cohort, while three cis- and seven trans-pQTLs were identified in the Dutch cohort. However, we observed minimal overlap (< 2%) in pQTLs between the two populations, with colocalization analysis confirming only nine shared loci. Additionally, we replicated several pQTLs identified in the UK-BIOBANK study across African and European ancestries. These findings underscore the genetic diversity underlying inflammatory protein regulation and highlight the importance of population-specific studies to better understand immune function, disease susceptibility, and tailored health interventions across diverse ancestries.