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Review
. 2014 Jan 17:20:64-71.
doi: 10.12659/MSM.889754.

Epistatic effects of multiple receptor genes on pathophysiology of asthma - its limits and potential for clinical application

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Review

Epistatic effects of multiple receptor genes on pathophysiology of asthma - its limits and potential for clinical application

Takahiro Yoshikawa et al. Med Sci Monit. .

Abstract

To date, genome-wide association studies (GWAS) permit a comprehensive scan of the genome in an unbiased manner, with high sensitivity, and thereby have the potential to identify candidate genes for the prevalence or development of multifactorial diseases such as bronchial asthma. However, most studies have only managed to explain a small additional percentage of hereditability estimates, and often fail to show consistent results among studies despite large sample sizes. Epistasis is defined as the interaction between multiple different genes affecting phenotypes. By applying epistatic analysis to clinical genetic research, we can analyze interactions among more than 2 molecules (genes) considering the whole system of the human body, illuminating dynamic molecular mechanisms. An increasing number of genetic studies have investigated epistatic effects on the risk for development of asthma. The present review highlights a concept of epistasis to overcome traditional genetic studies in humans and provides an update of evidence on epistatic effects on asthma. Furthermore, we review concerns regarding recent trends in epistatic analyses from the perspective of clinical physicians. These concerns include biological plausibility of genes identified by computational statistics, and definition of the diagnostic label of 'physician-diagnosed asthma'. In terms of these issues, further application of epistatic analysis will prompt identification of susceptibility of diseases and lead to the development of a new generation of pharmacological strategies to treat asthma.

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Figure 1
Figure 1
Clinical application of gene-gene interactions (epistasis) focused on measurable and objective features. Epistasis is defined as the interaction between two different factors (gene-gene) affecting phenotypes. It seems reasonable for clinical application of epistatic analyses to focus on a specific measurable and objective feature among plausible functional or pathophysiological mechanisms. Please see the section entitled ‘Considerations about clinical application of epistatic analyses in asthma research – limits and potentials’.

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