Genome-wide association study identifies genes and networks that influence innate immune response in an age-specific manner in Drosophila melanogaster

Abstract

Background The innate immune response is an evolutionarily conserved process that is essential for survival in multicellular organisms. As individuals age, immune functions decline, a phenomenon known as immunosenescence, reducing one’s ability to fight infections. While immunosenescence is a universal feature of aging, the rate at which immune functions decline with age varies greatly among individuals and this variation has a genetic component. However, we have limited knowledge of the actual genes that contribute to this variation. Methods Here, we used 183 genetically distinct genotypes of the Drosophila Genetic Reference panel (DGRP) to assess their ability to clear an infection at one and five weeks of age. We then carried out a genome-wide association study (GWAS) to identify candidate genes that contribute to differences in immune responses among genotypes at each age. Results We found that, on average, the ability to clear infection declined by 70% with age. However, the effect of age on clearance ability varied significantly among genotypes. We identified a total of 242 single nucleotide polymorphisms (SNPs) and 107 candidate genes associated with variation in clearance ability. Polymorphisms in 48 genes were associated with clearance in 1 week old flies and fifty-nine genes were associated with clearance ability at 5 weeks of age. Only one gene, a G-coupled protein receptor, CG31760, was a candidate at both ages. Of the 107 candidate genes, 25 were mapped to genetic networks. Conclusion Our results identify candidate genes that could be targets for age-appropriate therapeutic treatments to maintain or restore immune function in the elderly.