Shifman et al. (2002) reported a highly significant association between a COMT haplotype (rs737865-rs4680-rs165599) and schizophrenia. Bray et al. (2003) demonstrated that this haplotype is associated with lower expression of COMT mRNA in postmortem human brain tissue; much of this effect was from SNP rs165599. Chen et al (2004) found a small effect of rs209603, a SNP at the P2 promoter region of MB-COMT, on COMT enzyme activity. A two-SNP haplotype (rs2097603-rs4680) and a 3-SNP combination (rs2097603-rs4680-rs165599) were reported to have a strong impact on prefrontal memory response (Meyer-Lindenberg et al., 2006). In addition, other haplotypes (rs740603-rs4680-rs174699 and rs933271-rs4680-rs174699) showed sex-specific effects for nicotine dependence in AA and EA populations (Beuten et al., 2006). Another study (Lohoff et al, 2008) reported association between haplotype rs737865-rs4680 and cocaine dependence in a primarily African-ancestry population (Lohoff et al.,2008). These SNPs map close to our significant haplotype; rs4680 forms part of the haplotype for which we observed the most interesting results also. Our observations in the EA population were consistent with the study by Stein et al. (Stein et al., 2005) who found
