Although no SNPs in BDNF reach genomewide significance in the schizophrenia GWAS, it is a gene that has been implicated in schizophrenia previously, particularly in relation to cognitive deficits associated with the disease22, as well as other psychiatric disorders23. Some studies have suggested that smoking might be a method by which people with schizophrenia alleviate cognitive difficulties, although other studies suggest cognition is worse in people with schizophrenia who smoke24. Furthermore, given the higher prevalence of smoking in populations with mental health problems, it is possible that the smoking initiation GWAS sample might be enriched for mental health problems compared to the general population, meaning that variants identified could be causally linked to these mental health problems rather than smoking. This result must therefore be interpreted with particular caution; the association between SNPs in the BDNF gene area and schizophrenia may reflect a causal association between smoking initiation and schizophrenia, but could also potentially be a pleiotropic effect, either via one of the already identified alternative pathways such as obesity or caffeine, or via another currently unidentified pathway. It was
