Submited on: 24 Sep 2010 02:38:23 AM GMT
Published on: 24 Sep 2010 07:28:52 AM GMT
 

  • Other Comments: In this paper, Bosse and colleagues put forth a series of specific hypotheses related to the genetics and genomics of lung function decline and chronic obstructive lung disease that they intend to test in an integrative genomic framework. The proposed studies are focused on candidate genes that have been implicated in the pathogenesis of COPD or lung function decline, with specific hypotheses related to the role of variants in these genes in relation to lung function decline and COPD, gene expression as a function of glucocorticoid and long acting beta-receptor agonist responsiveness, immune and multi-drug resistance pathways, and lung injury and repair. The work extends to replicating prior findings related to molecular (expression profiling) signatures of COPD and emphysema, asthma and lung cancer. This paper is well written, providing a fairly concise overview of the proposed studies. The rationale for these studies is sound, with supporting evidence for the choice of candidates well referenced. In fact, this paper presents a very nice summary of the current state of COPD genetics. The approaches proposed are reasonable, though there is very little description of the statistical approaches that will be used for these varied (and at times) complex analyses. One issue that is not addressed is what will come of the excellent resources the team has put together once these initial hypotheses are tested. It is quite likely that additional research questions would be raised, leading to new hypotheses. The authors may wish to address how they will handle the multiple comparisons issues in such future studies.
  • Competing interests:
    None
  • Invited by the author to review this article? :
    Yes
  • Have you previously published on this or a similar topic?:
    Yes
  • References:
    Murphy A, Chu JH, Xu M, Carey VJ, Lazarus R, Liu A, Szefler SJ, Strunk R, Demuth K, Castro M, Hansel NN, Diette GB, Vonakis BM, Franklin Adkinson N Jr, Klanderman BJ, Senter-Sylvia J, Ziniti J, Lange C, Pastinen T, Raby BA. Mapping of numerous disease-associated expression polymorphisms in primary peripheral blood CD4+ lymphocytes. Hum Mol Genet. 2010 Oct 4. PubMed PMID: 20833654.
  • Experience and credentials in the specific area of science:
    Pulmonologist and geneticist with expertise in GWAS and eQTL mapping association in asthma and COPD.
  • How to cite:  Raby B .Review of Hypothesis-driven Research On Genomic Data Derived From A Large Scale Lung EQTL Mapping Study[Review of the article 'Hypothesis-driven Research on Genomic Data Derived from a Large Scale Lung EQTL Mapping Study ' by Pare P].WebmedCentral 2010;1(11):WMCRW00120
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  • Other Comments: In this paper, Bosse and colleagues put forth a series of specific hypotheses related to the genetics and genomics of lung function decline and chronic obstructive lung disease that they intend to test in an integrative genomic framework. The proposed studies are focused on candidate genes that have been implicated in the pathogenesis of COPD or lung function decline, with specific hypotheses related to the role of variants in these genes in relation to lung function decline and COPD, gene expression as a function of glucocorticoid and long acting beta-receptor agonist responsiveness, immune and multi-drug resistance pathways, and lung injury and repair. The work extends to replicating prior findings related to molecular (expression profiling) signatures of COPD and emphysema, asthma and lung cancer. This paper is well written, providing a fairly concise overview of the proposed studies. The rationale for these studies is sound, with supporting evidence for the choice of candidates well referenced. In fact, this paper presents a very nice summary of the current state of COPD genetics. The approaches proposed are reasonable, though there is very little description of the statistical approaches that will be used for these varied (and at times) complex analyses. One issue that is not addressed is what will come of the excellent resources the team has put together once these initial hypotheses are tested. It is quite likely that additional research questions would be raised, leading to new hypotheses. The authors may wish to address how they will handle the multiple comparisons issues in such future studies.
  • Competing interests:
    No
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    Yes
  • References:
    Murphy A, Chu JH, Xu M, Carey VJ, Lazarus R, Liu A, Szefler SJ, Strunk R, Demuth K, Castro M, Hansel NN, Diette GB, Vonakis BM, Franklin Adkinson N Jr, Klanderman BJ, Senter-Sylvia J, Ziniti J, Lange C, Pastinen T, Raby BA. Mapping of numerous disease-associated expression polymorphisms in primary peripheral blood CD4+ lymphocytes. Hum Mol Genet. 2010 Oct 4. PubMed PMID: 20833654.
  • Experience and credentials in the specific area of science:
    Pulmonologist and geneticist with expertise in GWAS and eQTL mapping association in asthma and COPD.
  • How to cite:  Raby B .Review of Hypothesis-driven Research On Genomic Data Derived From A Large Scale Lung EQTL Mapping Study[Review of the article 'Hypothesis-driven Research on Genomic Data Derived from a Large Scale Lung EQTL Mapping Study ' by Pare P].WebmedCentral 2010;1(11):WMCRW00113
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  • Other Comments: This is an interesting report that provides hypotheses to be tested in future study. The hypotheses are based on ~1200 subjects with both gene expression and SNP genotypes at the genomewide level. These valuable data will certainly ensure high dimensional correlation analysis between gene expression and SNP genotypes. The eQTL mapping has been emerging as a powerful tool for interpreting GWAS signals. However, the report will not be complete without clarifying the following concerns: 1. The report should describe distribution of clinical phenotypes for the 1200 individuals. This will be a key to evaluate the feasibility of the study design. I am assuming that each hypothesis will be based on a subgroup. Do these subgroups have enough patients to generate meaningful results? Please provide statistical power for the proposed studies. 2. The report should provide the necessary information on how to perform the different analyses. The report listed many hypotheses to be tested but lacked strategies on how to test them. For example, types of SNPs should be selected for eQTL analysis (e.g., distance to the candidate genes and allele frequency).
  • Competing interests:
    No
  • Invited by the author to review this article? :
    Yes
  • Have you previously published on this or a similar topic?:
    Yes
  • References:
    None
  • Experience and credentials in the specific area of science:
    None
  • How to cite:  Yang P .Hypothesis-driven Research on Genomic Data Derived from a Large Scale Lung EQTL Mapping Study[Review of the article 'Hypothesis-driven Research on Genomic Data Derived from a Large Scale Lung EQTL Mapping Study ' by Pare P].WebmedCentral 2010;1(10):WMCRW0086
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