- PLoS One
- v.8(9); 2013
- PMC3767824
PLoS One. 2013; 8(9): e73157.
Published online Sep 9, 2013. doi: 10.1371/journal.pone.0073157
PMCID: PMC3767824
María Pino-Yanes,1,2,¤ Almudena Corrales,1,2 José Cumplido,3 Paloma Poza,4 Inmaculada Sánchez-Machín,4Anselmo Sánchez-Palacios,5 Javier Figueroa,5 Orlando Acosta-Fernández,6 Nisa Buset,7 José Carlos García-Robaina,8 Mariano Hernández,9 Jesús Villar,1,7,10 Teresa Carrillo,3 and Carlos Flores1,2,9,*
Gualtiero I. Colombo, Editor
This article has been corrected. See PLoS One. 2013 September 13; 8(9): 10.1371/annotation/4d0bcb4c-ade9-4393-918f-daa5e7e5f6f6.
This article has been cited by other articles in PMC.
Abstract
Background
Before the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (aliasFCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis.
Methodology/Principal Findings
We systematically evaluated 286 common single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that variants atMS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition,in silico replication with GWAS data supported the association of IL4R.
Conclusions/Significance
Our results support the important role of MS4A2, IL4R and ADAM33 genes in asthma and/or atopy susceptibility. However, additional studies in larger samples sets are needed to firmly implicate these genes in asthma susceptibility, and also to identify the causal variation underlying the associations found.
Abstract
Background
Before the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (aliasFCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis.
Methodology/Principal Findings
We systematically evaluated 286 common single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that variants atMS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition,in silico replication with GWAS data supported the association of IL4R.
Conclusions/Significance
Our results support the important role of MS4A2, IL4R and ADAM33 genes in asthma and/or atopy susceptibility. However, additional studies in larger samples sets are needed to firmly implicate these genes in asthma susceptibility, and also to identify the causal variation underlying the associations found.
Abstract
Background
Before the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (aliasFCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis.
Methodology/Principal Findings
We systematically evaluated 286 common single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that variants atMS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition,in silico replication with GWAS data supported the association of IL4R.
Conclusions/Significance
Our results support the important role of MS4A2, IL4R and ADAM33
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