title: Identification of Susceptibility Genes of Adult Asthma in French Canadian Women.
abstract: Susceptibility genes of asthma may be more successfully identified by studying subgroups of phenotypically similar asthma patients. This study aims to identify single nucleotide polymorphisms (SNPs) associated with asthma in French Canadian adult women. A pooling-based genome-wide association study was performed in 240 allergic asthmatic and 120 allergic nonasthmatic women. The top associated SNPs were selected for individual genotyping in an extended cohort of 349 asthmatic and 261 nonasthmatic women. The functional impact of asthma-associated SNPs was investigated in a lung expression quantitative trait loci (eQTL) mapping study (n = 1035). Twenty-one of the 38 SNPs tested by individual genotyping showed P values lower than 0.05 for association with asthma. Cis-eQTL analyses supported the functional contribution of rs17801353 associated with C3AR1 (P = 7.90E - 10). The asthma risk allele for rs17801353 is associated with higher mRNA expression levels of C3AR1 in lung tissue. In silico functional characterization of the asthma-associated SNPs also supported the contribution of C3AR1 and additional genes including SYNE1, LINGO2, and IFNG-AS1. This pooling-based GWAS in French Canadian adult women followed by lung eQTL mapping suggested C3AR1 as a functional locus associated with asthma. Additional susceptibility genes were suggested in this homogenous subgroup of asthma patients.
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada G1V 4G5.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Bérubé
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada G1V 4G5.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gaudreault
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada G1V 4G5.
authors.forename: Emilie
authors.initials: E
authors.lastname: Lavoie-Charland
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada G1V 4G5.
authors.forename: Laura
authors.initials: L
authors.lastname: Sbarra
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada G1V 4G5.
authors.forename: Cyndi
authors.initials: C
authors.lastname: Henry
authors.affiliation: Département des Sciences Fondamentales, Université du Québec à Chicoutimi, Chicoutimi, QC, Canada G7H 2B1.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Madore
authors.affiliation: The University of British Columbia Center for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada; University of British Columbia Department of Medicine, Division of Respiratory Medicine, Vancouver, BC, Canada V5Z 1M9.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.affiliation: University Medical Center Groningen, GRIAC Research Institute, University of Groningen, Groningen, Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Berge
authors.affiliation: Merck Research Laboratories (MRL), Seattle, WA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Nickle
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada G1V 4G5.
authors.forename: Michel
authors.initials: M
authors.lastname: Laviolette
authors.affiliation: Département des Sciences Fondamentales, Université du Québec à Chicoutimi, Chicoutimi, QC, Canada G7H 2B1.
authors.forename: Catherine
authors.initials: C
authors.lastname: Laprise
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada G1V 4G5.
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada G1V 4G5; Department of Molecular Medicine, Laval University, Quebec City, QC, Canada G1V 0A6.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
mesh_terms: D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000378:metabolism; D002170:Canada; D016022:Case-Control Studies; D005260:Female; D005602:France / Q000208:ethnology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D008168:Lung / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D055815:Young Adult