title: 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.
authors.affiliation: Pfizer WRD, Human Genetics and Computational Biomedicine, The Portway Building, Granta Park, Cambridge CB21 6GS, UK.
authors.forename: Amy V
authors.initials: AV
authors.lastname: Jones
authors.affiliation: Pfizer WRD, Pharmatherapeutics Clinical R&D, Precision Medicine, 300 Technology Square Fl #3, Cambridge, MA 02139, USA.
authors.forename: Mera
authors.initials: M
authors.lastname: Tilley
authors.affiliation: Pfizer WRD, Computational Sciences CoE, The Portway Building, Granta Park, Cambridge CB21 6GS, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Gutteridge
authors.affiliation: Pfizer WRD, Research Statistics, 558 Eastern Point Rd, Groton, CT 06340, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Hyde
authors.affiliation: Pfizer WRD, Human Genetics and Computational Biomedicine, 610 Main Street S, Cambridge, MA 02139, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Nagle
authors.affiliation: Pfizer WRD, Computational Sciences CoE, Linkstraße 10, 10785 Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ziemek
authors.affiliation: Pfizer WRD, Research Statistics, The Portway Building, Granta Park, Cambridge CB21 6GS, UK.
authors.forename: Donal
authors.initials: D
authors.lastname: Gorman
authors.affiliation: Pfizer WRD, Computational Sciences CoE, 610 Main Street S, Cambridge, MA 02139, USA.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Fauman
authors.affiliation: Pfizer WRD, Research Statistics, 558 Eastern Point Rd, Groton, CT 06340, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Pfizer WRD, Human Genetics and Computational Biomedicine, 610 Main Street S, Cambridge, MA 02139, USA.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Miller
authors.affiliation: 23andMe, Inc, 899 W Evelyn Avenue, Mountain View, California, CA 94043, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Tian
authors.affiliation: 23andMe, Inc, 899 W Evelyn Avenue, Mountain View, California, CA 94043, USA.
authors.forename: Youna
authors.initials: Y
authors.lastname: Hu
authors.affiliation: 23andMe, Inc, 899 W Evelyn Avenue, Mountain View, California, CA 94043, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hinds
authors.affiliation: Pfizer Ltd, Neuroscience and Pain Research Unit, The Portway Building, Granta Park, Cambridge CB21 6GS, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Cox
authors.affiliation: Pfizer WRD, Human Genetics and Computational Biomedicine, The Portway Building, Granta Park, Cambridge CB21 6GS, UK.
authors.forename: Serena
authors.initials: S
authors.lastname: Scollen
mesh_terms: D000818:Animals; D009033:Culicidae / Q000235:genetics / Q000472:pathogenicity; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007299:Insect Bites and Stings / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011537:Pruritus / Q000235:genetics* / Q000473:pathology; D057566:Self Report; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism