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Chunk #8 — Online Methods — Lung eQTL analysis

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Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.
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Twenty-one out of the 22 SNPs (in main manuscript Table 1) were genotyped or imputed in the three cohorts, i.e. Laval, UBC, and Groningen. One of the SNPs, rs7186831, was not well-imputed; a proxy, rs11865296 in modest linkage disequilibrium (r2 = 0.54, 1000 genomes phase 3, EUR) was used instead. These variants were tested for association with adjusted expression traits (43,465 probe sets) in the lung. SNPs within 1 Mb up and downstream of the transcription probe set were considered as local-eQTL. Distant-acting eQTLs were further than 1 Mb away or on a different chromosome. Association tests were carried with PLINK1.964,65 in each cohort and then meta-analyzed using Fisher’s method. All local eQTL with nominal P value < 0.05 in the meta-analysis were considered. To provide an additional overall estimate of eQTL significance, we considered a Bonferroni correction threshold ([0.05/(22 SNPs × 43,465 probe sets) = P value < 5.2 × 10−8]). Statistical analyses were performed in R3.2.366.