Identification of Susceptibility Genes of Adult Asthma in French Canadian Women

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...

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Main Authors: Jean-Christophe Bérubé, Nathalie Gaudreault, Emilie Lavoie-Charland, Laura Sbarra, Cyndi Henry, Anne-Marie Madore, Peter D. Paré, Maarten van den Berge, David Nickle, Michel Laviolette, Catherine Laprise, Louis-Philippe Boulet, Yohan Bossé
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Canadian Respiratory Journal
Online Access:http://dx.doi.org/10.1155/2016/3564341
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author Jean-Christophe Bérubé
Nathalie Gaudreault
Emilie Lavoie-Charland
Laura Sbarra
Cyndi Henry
Anne-Marie Madore
Peter D. Paré
Maarten van den Berge
David Nickle
Michel Laviolette
Catherine Laprise
Louis-Philippe Boulet
Yohan Bossé
author_facet Jean-Christophe Bérubé
Nathalie Gaudreault
Emilie Lavoie-Charland
Laura Sbarra
Cyndi Henry
Anne-Marie Madore
Peter D. Paré
Maarten van den Berge
David Nickle
Michel Laviolette
Catherine Laprise
Louis-Philippe Boulet
Yohan Bossé
author_sort Jean-Christophe Bérubé
collection DOAJ
description 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.
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spelling doaj-art-83062a9100974955be3737c98d7a5cd32025-08-20T02:08:46ZengWileyCanadian Respiratory Journal1198-22411916-72452016-01-01201610.1155/2016/35643413564341Identification of Susceptibility Genes of Adult Asthma in French Canadian WomenJean-Christophe Bérubé0Nathalie Gaudreault1Emilie Lavoie-Charland2Laura Sbarra3Cyndi Henry4Anne-Marie Madore5Peter D. Paré6Maarten van den Berge7David Nickle8Michel Laviolette9Catherine Laprise10Louis-Philippe Boulet11Yohan Bossé12Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, G1V 4G5, CanadaInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, G1V 4G5, CanadaInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, G1V 4G5, CanadaInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, G1V 4G5, CanadaInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, G1V 4G5, CanadaDépartement des Sciences Fondamentales, Université du Québec à Chicoutimi, Chicoutimi, QC, G7H 2B1, CanadaThe University of British Columbia Center for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC, CanadaUniversity Medical Center Groningen, GRIAC Research Institute, University of Groningen, Groningen, NetherlandsMerck Research Laboratories (MRL), Seattle, WA, USAInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, G1V 4G5, CanadaDépartement des Sciences Fondamentales, Université du Québec à Chicoutimi, Chicoutimi, QC, G7H 2B1, CanadaInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, G1V 4G5, CanadaInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, G1V 4G5, CanadaSusceptibility 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.http://dx.doi.org/10.1155/2016/3564341
spellingShingle Jean-Christophe Bérubé
Nathalie Gaudreault
Emilie Lavoie-Charland
Laura Sbarra
Cyndi Henry
Anne-Marie Madore
Peter D. Paré
Maarten van den Berge
David Nickle
Michel Laviolette
Catherine Laprise
Louis-Philippe Boulet
Yohan Bossé
Identification of Susceptibility Genes of Adult Asthma in French Canadian Women
Canadian Respiratory Journal
title Identification of Susceptibility Genes of Adult Asthma in French Canadian Women
title_full Identification of Susceptibility Genes of Adult Asthma in French Canadian Women
title_fullStr Identification of Susceptibility Genes of Adult Asthma in French Canadian Women
title_full_unstemmed Identification of Susceptibility Genes of Adult Asthma in French Canadian Women
title_short Identification of Susceptibility Genes of Adult Asthma in French Canadian Women
title_sort identification of susceptibility genes of adult asthma in french canadian women
url http://dx.doi.org/10.1155/2016/3564341
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