Genome wide screening

Initial genome wide analysis of DNA in discovery database (n = 3500 heavy smokers at high-risk to develop COPD, Nelson study).  The initial genome wide analysis for association will consist of genotyping  approximately 300.000 tag SNPs on arrays from Illumina.  A simple statistical analysis shows that for ~ 300.000 SNPs genotyped in the cohort  at p < 0.01  400 SNPs would be positive. Some of these positive SNPs are truly different, some are false positives.

Validation of the ~ 400 most significant SNPs resulting form the initials genome wide analysis will be validated in the replication databases (Danish Copenhagen City Heart Study-cohort [n = 1.220 COPD subjects, n = 6.900 controls], Polish Krakow-cohort [n = 134 COPd subjects, n = 353 controls], Dutch Vlagtwedde/Vlaardingen cohort [n = 633 COPD subjects, n = 1738 controls], Heidelberg-cohort [~ 2.000 subjects to be included] and Euroscop-cohort [n = 700 COPD subjects, n = 500 controls]) to eliminate false positive SNPs.

Selection of approximately 30 most significant SNPs. 

More information about the other techniques used:

• CT scan
• Pulmonary function tests