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18 February 2014: Letter to the Editor  

Letter to the Editor regarding: Epistatic effects in pathophysiology of asthma and the “missing heritability” of this disease

Andrzej Brodziak ADEF , Piotr Z. Brewczyński ADFG

DOI: 10.12659/MSM.890506

Med Sci Monit 2014; 20:274-275

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Abstract

ABSTRACT: The authors of the letter try  to assess the importance of Yoshikawa's paper  presenting so-called epistatic effects and analyses as a tool  useful for explanation of the genetic  conditioning of asthma. They note that the investigations  of the genetic determinants of other chronic diseases such as atherosclerosis, coronary artery disease and Parkinson's disease also encountered epistatic effects. The authors of the letter state that,  in  fact,  the epistatic analyses it  is one of possible endeavors, which try to explain so called "missing heritability".   They enumerate other recognized mechanisms, which are proposed that explain the missing heritability. The authors of the letter appreciate the conclusions of Yoskikawa's  team important for clinicians. They emphasize that really asthma is a clinical condition that is diagnosed or suspected in course of occurrence of symptoms, which not allow unequivocally to diagnose this disease. In such circumstances the precise recognition of the specific genetic profile of a patient  (his status of  expression of genes recognized as pathogenic, as well as the  epistatic interactions) will improve the possibilities of treatment and prevention. The authors of the letter postulate  however,  that this practical diagnostic approach must be continually modified in course of the future trials of explanations of reasons of the discussed "missing heritability".

Keywords: Epistasis, Genetic - genetics, Asthma - physiopathology, Models, Biological, Phenotype, Receptors, Immunologic - genetics, Signal Transduction - immunology

References

1. Yoshikawa T, Kanazawa H, Fujimoto S, Hirata K, Epistatic effects of multiple receptor genes on pathophysiology of asthma – its limits and potential for clinical application: Med Sci Monit, 2014; 20; 64-71, pmid: 24435185

2. Eichler EE, Flint J, Gibson G, Missing heritability and strategies for finding the underlying causes of complex disease: Nat Rev Genet, 2010; 11; 446-50, pmid: 20479774

3. Keller MF, Saad M, Bras J, Using genome-wide complex trait analysis to quantify ‘missing heritability’ in Parkinson’s disease: Hum Mol Genet, 2012; 21; 4996-5009, pmid: 22892372

4. Marian AJ, The enigma of genetics etiology of atherosclerosis in the post-GWAS era: Curr Atheroscler Rep, 2012; 14; 295-99, pmid: 22437283

5. Marian AJ, Elements of ‘missing heritability’: Curr Opin Cardiol, 2012; 27; 197-201, pmid: 22450721

6. Manolio TA, Collins FS, Cox NJ, Finding the missing heritability of complex diseases: Nature, 2009; 461(7265); 747-53, pmid: 19812666

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Medical Science Monitor eISSN: 1643-3750