Serotonin transporter gene and schizophrenia: evidence for association/linkage disequilibrium in families with affected siblings

The serotonergic (5-HT) system has been implicated in the etiopathogenesis of psychoses. Since the 5-HT transporter plays an important role in regulat ion of 5-HT transmission, its gene can be considered as a candidate for vul nerability to psychiatric disorders. Two polymorphic sites of the 5-HT tran sporter gene-5-HTTLPR, a VNTR in the 5' regulatory region, and a VNTR in th e second intron-were studied in a sample of 61 families with schizophrenia for transmission disequilibrium. Each family contained at least two sibling s affected with schizophrenia or schizoaffective disorder (mainly schizophr enic). One hundred and thirty-nine affected offspring with parental informa tion for genotyping, were available for analysis. No preferential transmiss ion of either short or long alleles of the promoter polymorphism was observ ed. However, a transmission distortion was detected for alleles of the intr onic VNTR polymorphism (chi(TDT max)(2) =14.33; P = 0.0002; corrected P Val ue = 0.0003) resulting in more frequent than expected transmission of the 1 2 repeat allele, This finding adds additional evidence to the idea that the serotonergic system may be involved in development of psychoses.