Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.

<h4>Background</h4>The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking.<h4>Methodology/principal findings</h4>...

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Autores principales:	Ming-Wei Su, Kuan-Yen Tung, Pi-Hui Liang, Ching-Hui Tsai, Nai-Wei Kuo, Yungling Leo Lee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6f56ed6d73cb490d96718b2a47b8aae6
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spelling	oai:doaj.org-article:6f56ed6d73cb490d96718b2a47b8aae62021-11-18T07:28:15ZGene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.1932-620310.1371/journal.pone.0030694https://doaj.org/article/6f56ed6d73cb490d96718b2a47b8aae62012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22355322/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking.<h4>Methodology/principal findings</h4>We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 single-nucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR) method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1), the gene coding interleukin-4 receptor alpha chain (IL4Ra) and the gene coding insulin induced gene 2 (INSIG2) on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83% with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2), signal transducer and activator of transcription 6 (STAT6). We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance.<h4>Conclusions/significance</h4>The results of this study suggest that GSTP1, INSIG2 and IL4Ra may influence the lifetime asthma susceptibility through gene-gene interactions in schoolchildren. Home dampness combined with each one of the genes STAT6, IL13 and ADRB2 could raise the asthma risk.Ming-Wei SuKuan-Yen TungPi-Hui LiangChing-Hui TsaiNai-Wei KuoYungling Leo LeePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e30694 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ming-Wei Su Kuan-Yen Tung Pi-Hui Liang Ching-Hui Tsai Nai-Wei Kuo Yungling Leo Lee Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.
description	<h4>Background</h4>The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking.<h4>Methodology/principal findings</h4>We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 single-nucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR) method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1), the gene coding interleukin-4 receptor alpha chain (IL4Ra) and the gene coding insulin induced gene 2 (INSIG2) on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83% with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2), signal transducer and activator of transcription 6 (STAT6). We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance.<h4>Conclusions/significance</h4>The results of this study suggest that GSTP1, INSIG2 and IL4Ra may influence the lifetime asthma susceptibility through gene-gene interactions in schoolchildren. Home dampness combined with each one of the genes STAT6, IL13 and ADRB2 could raise the asthma risk.
format	article
author	Ming-Wei Su Kuan-Yen Tung Pi-Hui Liang Ching-Hui Tsai Nai-Wei Kuo Yungling Leo Lee
author_facet	Ming-Wei Su Kuan-Yen Tung Pi-Hui Liang Ching-Hui Tsai Nai-Wei Kuo Yungling Leo Lee
author_sort	Ming-Wei Su
title	Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.
title_short	Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.
title_full	Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.
title_fullStr	Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.
title_full_unstemmed	Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.
title_sort	gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/6f56ed6d73cb490d96718b2a47b8aae6
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Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.

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