AbstractThe expression of serotonin type 6 receptor (5‐HT6) in limbic and cortical regions of the brain, and its high affinity for atypical antipsychotics suggest that its encoding gene may play a role in the pathogenesis of schizophrenia. We firstly performed a meta‐analysis of the C267T polymorphism of the 5‐HT6 gene in schizophrenia, based on four different case/control studies, and showed that the allelic distribution is not significantly different between patients and controls, even when taking into account the role of between samples heterogeneity. We then recruited 103 trios (patients with Diognostic and Statistical Manual Mental Disorders, 4th ed. (DSM‐IV) diagnosis of schizophrenia and their parents), and investigated the C267T polymorphism of the 5‐HT6 receptor gene with regard to family‐based association study approach (haplotype relative risk (HRR) and transmission disequilibrium test (TDT)). We found no excess of transmission of one allele from the parents to their affected children, using the HRR (P = 0.60), as well as no evidence for linkage between C267T polymorphism and schizophrenia, using the TDT (P = 0.71). Furthermore, the 267T allele frequency was comparable in the different subgroups defined on age at onset, family history of schizophrenia, treatment response, and subtypes of patients based on positive versus negative predominant symptoms. These data do not support the idea that the 5‐HT6 receptor gene plays a major role in the etiopathogenesis of schizophrenia. © 2003 Wiley‐Liss, Inc.