title: Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Su
authors.forename: Kuan-Yen
authors.initials: KY
authors.lastname: Tung
authors.forename: Pi-Hui
authors.initials: PH
authors.lastname: Liang
authors.forename: Ching-Hui
authors.initials: CH
authors.lastname: Tsai
authors.forename: Nai-Wei
authors.initials: NW
authors.lastname: Kuo
authors.forename: Yungling Leo
authors.initials: YL
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D004247:DNA / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D058011:Multifactor Dimensionality Reduction; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology
chemical_list: C504000:IL4R protein, human; C467727:INSIG2 protein, human; D053662:Interleukin-4 Receptor alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D004247:DNA; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi