Investigating residual confounding from smoking on the relationship between fasting glucose and lung function

We investigated whether a residual effect of smoking could confound the link between glucose and lung function. Firstly, we selected two well-powered GWAS of smoking behaviours: ever vs. never smoked (N = 385,013) (Watanabe et al., 2019) and cigarettes smoked per day (N = 263,954) (Liu et al., 2019). Genetic correlation between these two smoking phenotypes and fasting glucose was estimated as described above, followed by the construction of an LCV model. The MR IVs utilised for fasting glucose were also checked for association with each smoking GWAS. We also probed whether there could be an effect of collider bias in the event smoking does indeed exert an effect on fasting glucose. To this end the LCV and MR analyses was repeated for fasting glucose using smaller UK Biobank GWAS of FEV₁ and FVC from the Neale Lab as it was not adjusted for smoking (N = 272,338, http://www.nealelab.is/uk-biobank).