title: Genome-wide association study of antibody responses to Plasmodium falciparum candidate vaccine antigens.
abstract: We conducted a genome-wide association study (GWAS) of antibody responses directed to three Plasmodium falciparum vaccine candidate antigens (MSP1, MSP2 and GLURP) previously associated with different patterns of protection against malaria infection in Senegalese children. A total of 174 950 single-nucleotide polymorphisms (SNPs) were tested for association with immunoglobulin G1 (IgG1) responses directed to MSP1 and to GLURP and with IgG3 responses to MSP2 FC27 and to MSP2 3D7. We first performed a single-trait analysis with each antibody response and then a multiple-trait analysis in which we analyzed simultaneously the three immune responses associated with the control of clinical malaria episodes. Suggestive associations (P<1 × 10(-4)) were observed for 25 SNPs in MSP1 antibody response analysis or in multiple-trait analysis. According to the strength of their observed associations and their functional role, the following genes are of particular interest: RASGRP3 (2p22.3, P=7.6 × 10(-6)), RIMS1 (6q13, P=2.0 × 10(-5)), MVB12B (9q33.3, P=8.9 × 10(-5)) and GNPTAB (12q23.2, P=7.4 × 10(-5)). Future studies will be required to replicate these findings in other African populations. This work will contribute to the elucidation of the host genetic factors underlying variable immune responses to P. falciparum.
authors.affiliation: Institut de Recherche pour le Développement, UMR 216 MERIT, Mère et Enfant Face aux Infections Tropicales, Paris, France.|COMUE Sorbonne Paris Cité, Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Milet
authors.affiliation: Institut de Recherche pour le Développement, UMR 216 MERIT, Mère et Enfant Face aux Infections Tropicales, Paris, France.|COMUE Sorbonne Paris Cité, Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Sabbagh
authors.affiliation: Institut de Recherche pour le Développement, UMR 216 MERIT, Mère et Enfant Face aux Infections Tropicales, Paris, France.|COMUE Sorbonne Paris Cité, Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Migot-Nabias
authors.affiliation: Institut de Recherche pour le Développement, UMR 216 MERIT, Mère et Enfant Face aux Infections Tropicales, Paris, France.|COMUE Sorbonne Paris Cité, Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: A J F
authors.initials: AJ
authors.lastname: Luty
authors.affiliation: Service de Parasitologie, Faculté de Médecine et Pharmacie, Dakar, Senegal.
authors.forename: O
authors.initials: O
authors.lastname: Gaye
authors.affiliation: Institut de Recherche pour le Développement, UMR 216 MERIT, Mère et Enfant Face aux Infections Tropicales, Paris, France.|COMUE Sorbonne Paris Cité, Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Garcia
authors.affiliation: Institut de Recherche pour le Développement, UMR 216 MERIT, Mère et Enfant Face aux Infections Tropicales, Paris, France.|COMUE Sorbonne Paris Cité, Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Courtin
mesh_terms: D000293:Adolescent; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D002648:Child; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000737:chemistry* / Q000276:immunology; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics; D017780:Malaria Vaccines / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000235:genetics* / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000276:immunology; D010963:Plasmodium falciparum / Q000737:chemistry / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology; D012675:Senegal
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; C072492:glutamate-rich protein, Plasmodium