Abstract
Understanding the interaction between humans and mosquitoes is a critical area of study due to the phenomenal burdens on public health from mosquito-transmitted diseases. In this study, we conducted the first genome-wide association studies (GWAS) of self-reported mosquito bite reaction size (n = 84,724), itchiness caused by bites (n = 69,057), and perceived attractiveness to mosquitoes (n = 16,576). In total, 15 independent significant (P < 5×10−8) associations were identified. These loci were enriched for immunity-related genes that are involved in multiple cytokine signalling pathways. We also detected suggestive enrichment of these loci in enhancer regions that are active in stimulated T-cells, as well as within loci previously identified as controlling central memory T-cell levels. Egger regression analysis between the traits suggests that perception of itchiness and attractiveness to mosquitoes is driven, at least in part, by the genetic determinants of bite reaction size.Our findings illustrate the complex genetic and immunological landscapes underpinning human interactions with mosquitoes.
Highlights
Being bitten by mosquitoes is a common, but generally minor irritation
We identified a high degree of pleiotropy between these traits, and our genome-wide association studies (GWAS) identified a collective total of 15 independent genome-wide significant (GWS) loci, all of which map to immune genes
We investigated the heritability of the measured traits by applying LD Score regression [11] on GWAS summary statistics to determine the fraction of heritability explained by the GWS loci (P < 5Â10À8) that were identified by each mosquito-trait GWAS (Supplementary Material, Table S16, Materials and Methods)
Summary
Being bitten by mosquitoes is a common, but generally minor irritation. mosquitoes are vectors for many infectious agents that affect humans and have the potential to transmit deadly diseases like malaria, dengue, yellow fever and Zika virus-associated microcephaly [1,2]. Mosquito bite size data were analysed by linear regression (Materials and Methods) and after applying quality controls we identified 10 GWS (P < 5Â10À8) associations, as illustrated in the Manhattan plot (Fig. 1).
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