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GWAS of self-reported mosquito bite size, itch intensity and attractiveness to mosquitoes implicates immune-related predisposition loci.

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.

SUBMITTER: Jones AV

PROVIDER: S-EPMC5390679 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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GWAS of self-reported mosquito bite size, itch intensity and attractiveness to mosquitoes implicates immune-related predisposition loci.

Jones Amy V AV Tilley Mera M Gutteridge Alex A Hyde Craig C Nagle Michael M Ziemek Daniel D Gorman Donal D Fauman Eric B EB Chen Xing X Miller Melissa R MR Tian Chao C Hu Youna Y Hinds David A DA Cox Peter P Scollen Serena S

Human molecular genetics 20170401 7

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 ...[more]

PMID: 28199695

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Project description:Blood-feeding mosquitoes locate humans spatially by detecting a combination of human-derived chemical signals, including carbon dioxide, lactic acid, and other volatile organic compounds. Mosquitoes use these signals to differentiate humans from other animals. Spatial abiotic factors (e.g. humidity, heat) are also used by mosquitoes to find a host. Mosquitoes cause discomfort and harm to humans, being vectors of many pathogens. However, not all humans suffer from mosquito bites with the same frequency or intensity. Some individuals are more attractive to mosquitoes than others, and this has an important impact on the risk of infection by pathogens transmitted by these vectors, such as arboviruses and malaria parasites. Variability in human attractiveness to mosquitoes is partially due to individual characteristics in the composition and intensity in the release of mosquito attractants. The factors that determine these particularities are diverse, modestly understood and still quite controversial. Thus, this review discusses the role of pregnancy, infection with malaria parasites (Plasmodium spp.), skin microbiota, diet, and genetics in human attractiveness to mosquitoes. In brief, pregnancy and Plasmodium infection increase the host attractiveness to mosquitoes. Skin microbiota and human genetics (especially HLA alleles) modulate the production of mosquito attractants and therefore influence individual susceptibility to these insects. There is evidence pointing to a role of diet on human susceptibility to mosquitoes, with some dietary components having a bigger influence than others. In the last part of the review, other factors affecting human-mosquito interactions are debated, with a special focus on the role of mosquito genetics, pathogens and environmental factors (e.g. wind, environmental disturbances). This work highlights that individual susceptibility to mosquitoes is composed of interactions of different human-associated components, environmental factors, and mosquito characteristics. Understanding the importance of these factors, and how they interact with each other, is essential for the development of better mosquito control strategies and studies focused on infectious disease dynamics.

Dataset Information

GWAS of self-reported mosquito bite size, itch intensity and attractiveness to mosquitoes implicates immune-related predisposition loci.

Publications

GWAS of self-reported mosquito bite size, itch intensity and attractiveness to mosquitoes implicates immune-related predisposition loci.

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