Identification of Susceptibility Genes of Adult Asthma in French Canadian Women

Autor: 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
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Canadian Respiratory Journal, Vol 2016 (2016)
Druh dokumentu: article
ISSN: 1198-2241
1916-7245
DOI: 10.1155/2016/3564341
Popis: 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.
Databáze: Directory of Open Access Journals
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