the sample to investigate whether this association is seen in non-smokers (indicating shared genetic aetiology of the two traits) or only in regular smokers (indicating a direct causal association). Whilst this SNP has been identified in unstratified GWAS of outcomes where a causal association with smoking is known (e.g., lung cancer), this has only been the case where effect sizes are sufficiently large that the association can survive this dilution. In order to glean more information about causality (versus direct biological pleiotropy, where the SNP in question has an effect on both smoking and schizophrenia), a stratified analysis would be required, to check for a lack of association in non-smokers. To perform a 2-sample analysis on the unstratified PGC2 GWAS would merely repeat what is already known from the GWAS, that this SNP is associated with schizophrenia risk, but would not help us understand causality.
