Dataset Information

Selection of genes for gene-environment interaction studies: a candidate pathway-based strategy using asthma as an example.

ABSTRACT:

Background

The identification of gene by environment (GxE) interactions has emerged as a challenging but essential task to fully understand the complex mechanism underlying multifactorial diseases. Until now, GxE interactions have been investigated by candidate approaches examining a small number of genes, or agnostically at the genome wide level.

Presentation of the hypothesis

In this paper, we propose a gene selection strategy for investigation of gene-environment interactions. This strategy integrates the information on biological processes shared by genes, the canonical pathways to which they belong and the biological knowledge related to the environment in the gene selection process. It relies on both bioinformatics resources and biological expertise.

Testing the hypothesis

We illustrate our strategy by considering asthma, tobacco smoke as the environmental exposure, and genes sharing the same biological function of "response to oxidative stress". Our filtering strategy leads to a list of 28 pathways involving 182 genes for further GxE investigation.

Implications of the hypothesis

By integrating the environment into the gene selection process, we expect that our strategy will improve the ability to identify the joint effects and interactions of environmental and genetic factors in disease.

SUBMITTER: Rava M

PROVIDER: S-EPMC3708788 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Publications

Selection of genes for gene-environment interaction studies: a candidate pathway-based strategy using asthma as an example.

Rava Marta M Ahmed Ismaïl I Demenais Florence F Sanchez Margaux M Tubert-Bitter Pascale P Nadif Rachel R

Environmental health : a global access science source 20130703

<h4>Background</h4>The identification of gene by environment (GxE) interactions has emerged as a challenging but essential task to fully understand the complex mechanism underlying multifactorial diseases. Until now, GxE interactions have been investigated by candidate approaches examining a small number of genes, or agnostically at the genome wide level.<h4>Presentation of the hypothesis</h4>In this paper, we propose a gene selection strategy for investigation of gene-environment interactions. ...[more]

PMID: 23822639

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Project description:BACKGROUND: Asthma genetics has been extensively studied and many genes have been associated with the development or severity of this disease. In contrast, the genetic basis of allergic rhinitis (AR) has not been evaluated as extensively. It is well known that asthma is closely related with AR since a large proportion of individuals with asthma also present symptoms of AR, and patients with AR have a 5-6 fold increased risk of developing asthma. Thus, the relevance of asthma candidate genes as predisposing factors for AR is worth investigating. The present study was designed to investigate if SNPs in highly replicated asthma genes are associated with the occurrence of AR. METHODS: A total of 192 SNPs from 21 asthma candidate genes reported to be associated with asthma in 6 or more unrelated studies were genotyped in a Swedish population with 246 AR patients and 431 controls. Genotypes for 429 SNPs from the same set of genes were also extracted from a Singapore Chinese genome-wide dataset which consisted of 456 AR cases and 486 controls. All SNPs were subsequently analyzed for association with AR and their influence on allergic sensitization to common allergens. RESULTS: A limited number of potential associations were observed and the overall pattern of P-values corresponds well to the expectations in the absence of an effect. However, in the tests of allele effects in the Chinese population the number of significant P-values exceeds the expectations. The strongest signals were found for SNPs in NPSR1 and CTLA4. In these genes, a total of nine SNPs showed P-values <0.001 with corresponding Q-values <0.05. In the NPSR1 gene some P-values were lower than the Bonferroni correction level. Reanalysis after elimination of all patients with asthmatic symptoms excluded asthma as a confounding factor in our results. Weaker indications were found for IL13 and GSTP1 with respect to sensitization to birch pollen in the Swedish population. CONCLUSIONS: Genetic variation in the majority of the highly replicated asthma genes were not associated to AR in our populations which suggest that asthma and AR could have less in common than previously anticipated. However, NPSR1 and CTLA4 can be genetic links between AR and asthma and associations of polymorphisms in NPSR1 with AR have not been reported previously.

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Dataset Information

Selection of genes for gene-environment interaction studies: a candidate pathway-based strategy using asthma as an example.

Background

Presentation of the hypothesis

Testing the hypothesis

Implications of the hypothesis

Publications

Selection of genes for gene-environment interaction studies: a candidate pathway-based strategy using asthma as an example.

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