Exploring pleiotropy in Mendelian randomisation analyses: What are genetic variants associated with “cigarette smoking initiation” really capturing?

This observational study examined whether there was evidence of horizontal pleiotropy for genetic variants associated at genome-wide significance with different smoking phenotypes. We conducted analyses using data from UK Biobank (N=101,397 to 336,988) and ALSPAC (mother N=3,635 to 13,093, father / partner N=1,713 to 9,833, child N=4,703 to 13,923). The analysis plan for this study was pre-registered on Open Science Framework (https://osf.io/37xyn).