Third, including multiple aspects of smoking behaviour could have introduced more potential for horizontal pleiotropy. The more diffuse the definition of smoking, the more lifestyle factors might be correlated, making it especially important to test for horizontal pleiotropy. We conducted multiple sensitivity analyses (which all make different and largely uncorrelated assumptions), and all demonstrated the same direction of effect. This increases our confidence that the results are not biased by pleiotropy. Furthermore, MR Egger intercepts did not show evidence of directional pleiotropy for schizophrenia or depression. However, further work should still attempt to understand the biological mechanisms underpinning the association to reduce the likelihood of pleiotropic effects.
