Investigating the relationship between circulating cytokine levels and West African Genetic Ancestry 4257

Description Genetic ancestry reflects evolutionary adaptations in metabolism, skin pigmentation, and immune responses. Pro-inflammatory interleukins and interferons are key mediators of chronic diseases disproportionately affecting Black/African Americans (B/AA). Investigating the relationship between genetic ancestry and cytokine profiles in admixed populations is crucial for addressing health disparities and identifying ancestry-specific inflammatory signatures. We analyzed genomic ancestry and cytokine profiles in 541 participants (188 men, 356 women) from metro-Atlanta in the Discovery of Us Project™. Genomic ancestry was determined using Agena Biosciences and Mass ARRAY technology to calculate West African Ancestry (WAA) proportions, which were categorized into low (<76%; N = 54), medium (81–86%; N = 95), and high (>87%; N = 53) groups. Serum inflammatory markers were quantified using xMAP Intelliflex technology. Statistical analyses included linear regression, ANOVA, and Tukey HSD tests to assess WAA associations with IL-4, IL-7, TNFα, and IFN? concentrations. We observed significant relationships between WAA and IL-4 (P = 0.037), IFN? (P = 0.018), and TNFα (P = 0.009). Trends were noted in IL-4 (P = 0.082) and IL-7 (P = 0.091) between low and high WAA groups. Higher WAA proportions were associated with elevated pro-inflammatory markers, suggesting genetic ancestry influences inflammatory signatures. Further studies on sex differences and larger B/AA cohorts are needed to explore these findings. Funding Sources This study has been supported by NIH/NCI U54CA118638 (JRJ) NIH KL2TR002381 (LWB), NIH UL1TR002378 (LWB), NIH R01MD017405 (KW, AG, KSK), and NIH/NIMHD Research Centers in Minority Institutions 2U54MD007602 (KW, RAK, TLJ, AG, JRJ, LWB, KSK).