Here we improve upon previous MR studies of smoking and mental health in two ways: (1) by using an updated instrument for smoking initiation which comprises 378 SNPs (Liu et al., 2019) and (2) we develop a novel genetic instrument for lifetime smoking exposure that takes into account smoking status (i.e. ever and never smokers), and among ever smokers takes into account smoking duration, heaviness and cessation. This instrument can therefore capture smoking behaviours beyond initiation and can be used in unstratified samples of smokers and non-smokers. By using the results of these different MR analyses together and triangulating across multiple methods, we aim to determine whether the observational associations between smoking, schizophrenia and depression are likely causal, and the directionality of these relationships.
