RE: question about incorporting genotyping data in disease progression model

From: Jakob Ribbing Date: August 29, 2012 technical Source: mail-archive.com
Hi Kehua, If I understand you correctly you screened thousands of genotypes to find those that appeared to be the (60 most) promising predictors? Were the asthma patients in your nonmem analysis part of the material you used for GWAS screen, or is the nonmem analysis based on external data from other patients that were not part of the initial screen? I also was not quite clear on whether the subsequent nonmem analysis was based on genotype or gene expression? Either way, if an external set of patients were not used in the nonmem analysis; that would be the reason you find so many significant covariates. Apologies if this was a trivial answer that was not relevant for your work, but there are many examples of this in the field of data mining, where the multiple testing has not been taken into account when declaring significance or claiming that a highly predictive model has been established. Best regards Jakob
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From: [email protected] [mailto:[email protected]] On Behalf Of kehua wu Sent: 29 August 2012 17:21 To: [email protected] Subject: [NMusers] question about incorporting genotyping data in disease progression model Dear NONMEM users, I am working on a model in asthma patients and trying to build a model of FEV1, which is the evaluation of lung function. I have 500,000 genotyping data. First, I screened the genotyping data by running GWAS to find out the potential genotyping data, which gave me about 60 genotypes. Then, I tried to add these 60 genotyping data into model to find out if the progress of FEV1 is related with gene expression. But the problem is that too many genotypes were related with a significant change in OFV, which does not sound reasonable to me. I was hoping to find few (2-3) genotypes are associated with the progress in lung function. I have tried to include the genotyping data as discrete covariate (if genotyping =1 then parameter=theta(1); if genotyping =2 then parameter=theta(2); if genotyping=3 then parameter =theta(3)), and power function (genotype**(theta)). Did I do something wrong when including the genotyping data in the model as covariate? Thanks a lot in advance! Kehua
Aug 29, 2012 Kehua wu question about incorporting genotyping data in disease progression model
Aug 29, 2012 Ahmed N Mohamed Re: question about incorporting genotyping data in disease progression model
Aug 29, 2012 Jakob Ribbing RE: question about incorporting genotyping data in disease progression model