GWAS of chronic bronchitis

Months have passed since I introduced myself to you. The first topic on my program was the GWAS of chronic bronchitis. I prepared myself for statistical analysis of whole genome data (PLINK) and have read the literature about COPD, especially chronic bronchitis. For this GWAS we use DNA and clinical data of the participants (Groningen and Utrecht) of the Nelson study, a lung cancer screening study. All participants of this study have smoked a lot! They are current and former smokers with at least 20 packyears. We selected all individuals with complete data of respiratory symptoms, lung function, CT scan and genotyping data (Illumina Human 610-Quad). In this way more than 2500 participants were evaluable. Because there remained only 5 women, we decided to exclude them. As you may know, the success of a GWAS depends on the accuracy of the phenotype. In the part of the research that I perform, this is determined by a positive answer on the question: do you suffer, at least 3 months a year, from cough and/or sputum expectoration (even when you do not have a cold). After analyzing the genotyping data for different case definitions — presence of both or just one of these symptoms — reviewing the QQ-plot of these analyses, we concluded that chronic mucus hypersecretion (CMH), expectoration of sputum during at least 3 months, was the stronger phenotype. Although we found no “GWA-significant-indication” we found many “almost significant” SNPs in and nearby SNPs with a putative role in CMH development. Now, the next step is replication of these SNPs in other cohorts. SNPs for replication have been ordered and in some weeks we expect to start with testing of these SNPs in the replication cohorts and then analyse the new data. These are exciting times!!