A total of 14 260 cases and 15 480 controls from the UK Biobank were included in the latest GWAS for major depression (Wray et al., 2018) which could lead to bias from sample overlap (Burgess et al., 2015). Therefore, this analysis was repeated using summary data from an earlier GWAS of major depression (Ripke et al., 2013), which showed a consistent direction of effect with weaker statistical evidence, possibly due to reduced sample size (N = 18 759) (see online Supplementary Table S7). Second, we repeated this analysis with the recent meta-analysed GWAS which includes broader definitions of depression including self-declared (Howard et al., 2019). These summary data were available with UK Biobank and 23andMe removed leaving a sample size of 500 199 (170 756 cases and 329 443 controls). The results of this analysis are presented in online Supplementary Table S11. They are relatively consistent with the main analysis, showing slightly larger effects of depression on smoking and slightly reduced effects of smoking on depression. Bi-directional MR analyses were repeated using the GWAS of lifetime smoking without controlling
