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Chunk #33 — Online Methods — Association testing and selection of signals from stage 1 for follow-up in stage 2

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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
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From each of the three discovery GWAS, signals were selected for follow-up in stage 2 if they met an initial threshold of P<5x10-7. Low MAC variants (MAC between 3 and 20), were selected for follow-up only if the imputation quality (info) exceeded 0.8. Independence of signals was determined as follows: the most strongly associated (P<5x10-7) variant within a 1Mb region was selected as a putative signal and then the analysis repeated for that 1Mb region conditioning on the most strongly associated variant. Any variant which then had a conditional P<5x10-7 was then assigned as a secondary putative signal and also included in the conditional analysis. This was repeated until no variants with P<5x10-7 remained within the 1Mb region. Results were confirmed using a joint conditional analysis (GCTA51) and visual inspection of region plots. Previously reported signals were not included in the final list of putative signals to be taken for follow-up in stage 2. Where novel signals for different traits were in linkage disequilibrium (r2 > 0.2), the variant for the trait with the most significant association was followed up.