COMT and schizophrenia: Moreover, while the vast majority of studies on COMT investigated the rs4680 genotype, the present study included COMT rs4680 and rs4818 polymorphisms, which is important because it was suggested that the COMT rs4818 polymorphism may be responsible for an even larger variation in the COMT activity than the rs4680 polymorphism [20], and that COMT haplotypes are associated with schizophrenia susceptibility [90].