Impact of Archaic Introgression on the Abundance of Circulating Inflammatory Proteins in Modern Humans

Abstract

Archaic introgression refers to the transfer of genetic material from archaic hominins such as Neanderthals into ancestors of modern humans. This admixture has left detectable introgressed variants in present-day human populations. Expanding studies suggest that these introgressed variants may affect the range of phenotypic traits, including immunity and inflammation. In this study, we investigated the effect of such introgressed alleles from Neanderthals on circulating inflammatory protein levels in plasma. To do so, we combined a curated archaic introgression map with genome-wide association summary statistics from protein quantitative trait loci (pQTL) studies. We identified 849 archaic SNPs that overlapped with the pQTL signals. From these, 21 archaic alleles, with the strongest association within 1Mb genomic regions, were chosen for further functional annotation. Two variants were found in regions linked to MMP10 and IL18 genes and several introgressed SNPs were associated with protein levels such as CCL25, TNF-β, CCL23, and CCL19 which are involved in autoimmune and inflammatory diseases. These findings contribute to the growing understanding of how archaic DNA continues to shape immune function in modern humans.