title: A targeted association study of immunity genes and networks suggests novel associations with placental malaria infection.
abstract: A large proportion of the death toll associated with malaria is a consequence of malaria infection during pregnancy, causing up to 200,000 infant deaths annually. We previously published the first extensive genetic association study of placental malaria infection, and here we extend this analysis considerably, investigating genetic variation in over 9,000 SNPs in more than 1,000 genes involved in immunity and inflammation for their involvement in susceptibility to placental malaria infection. We applied a new approach incorporating results from both single gene analysis as well as gene-gene interactions on a protein-protein interaction network. We found suggestive associations of variants in the gene KLRK1 in the single gene analysis, as well as evidence for associations of multiple members of the IL-7/IL-7R signalling cascade in the combined analysis. To our knowledge, this is the first large-scale genetic study on placental malaria infection to date, opening the door for follow-up studies trying to elucidate the genetic basis of this neglected form of malaria.
authors.affiliation: Institute of Evolutionary Biology (UPF-CSIC), CEXS-UPF-PRBB, Barcelona, Catalonia, Spain.
authors.forename: Martin
authors.initials: M
authors.lastname: Sikora
authors.forename: Hafid
authors.initials: H
authors.lastname: Laayouni
authors.forename: Clara
authors.initials: C
authors.lastname: Menendez
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.forename: Azucena
authors.initials: A
authors.lastname: Bardaji
authors.forename: Betuel
authors.initials: B
authors.lastname: Sigauque
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Ferran
authors.initials: F
authors.lastname: Casals
authors.forename: Jaume
authors.initials: J
authors.lastname: Bertranpetit
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D016778:Malaria, Falciparum / Q000235:genetics* / Q000469:parasitology; D010922:Placenta Diseases / Q000235:genetics* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000472:pathogenicity; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000235:genetics* / Q000469:parasitology
chemical_list: D015415:Biomarkers