In order to determine whether the association between smoking and schizophrenia is causal, conventional MR using SNPs associated with heaviness of smoking would be informative, if a large sample could be identified with information on both schizophrenia case status and smoking status. One study has attempted this using anti-psychotic medication as a proxy for schizophrenia17. They found weak evidence using MR that higher cigarette consumption amongst smokers was associated with increased likelihood of being on antipsychotic medication, although it is not possible to rule out a direct effect of the SNP (rs1051730) on the outcome from these data. In that study, the OR was substantially smaller in their sample of non-smokers, although confidence intervals overlapped substantially between the two analyses. It is also important to note that many individuals who are prescribed anti-psychotic medication do not have schizophrenia or a psychotic illness, and therefore this may not be an ideal proxy measure for schizophrenia30.
