Haplotype analysis confirms association of the serotonin transporter (5-HTT) gene with schizophrenia but not with major depression†

Serotonin (5-HT) has been implicated in the pathophysiology of several psychiatric disorders including major depressive disorder (MDD) and schizophrenia (SCZ). The serotonin transporter (5-HTT) is a major regulator of 5-HT function. 5-HTT gene polymorphic variants have been associated with both MDD and SCZ. A case–control design was used for candidate gene-disease association in 194 MDD patients, 155 schizophrenic psychosis patients, and 246 healthy controls, all North European Caucasians. Four polymorphisms were analyzed in terms of genotype, allele, and haplotype-based associations. Linkage disequilibrium (LD) analysis was also carried out. Bonferroni correction was used for multiple testing. Haplotype-based analyses showed significant associations between 5-HTT and SCZ but not MDD. No single locus associations were observed. In agreement with published meta-analysis our results indicate that 5-HTT associates with SCZ but not with MDD. It appears that risk for SCZ maps within a specific 5-HTT haplotype block. © 2007 Wiley-Liss, Inc.