Genome-wide association data provide further support for an association between 5-HTTLPR and major depressive disorder

Abstract

BackgroundDysfunctions of serotonergic neurotransmission are supposed to be involved in the pathogenesis of psychiatric disorders such as major depressive disorder (MDD). The concentration of serotonin (5-hydroxytryptamine, 5-HT) in the synaptic cleft is essentially regulated by the 5-HT transporter (5-HTT). A length polymorphism repeat in the 5-HTT promoter region, termed 5-HTTLPR, has been commonly investigated for an association with psychiatric disorders. MethodsGenotyping of the 5-HTTLPR is time-consuming and technically challenging. Recently, a two-SNP haplotype was identified that tags the 5-HTTLPR at r2=0.775. This allows extraction of 5-HTTLPR genotype information from large genome-wide association study (GWAS) data sets. In the present study we performed haplotype analysis using a German GWAS case-control dataset to test for an association between MDD and the two-SNP tagging haplotype for 5-HTTLPR. ResultsWe detected a significant association between the TA haplotype (tagging the S-allele of the 5-HTTLPR) and MDD. Our result is consistent with previous findings of an association between the 5-HTTLPR S-allele and MDD. LimitationsUsing the two-SNP tagging haplotype did not allow testing of the tri-allelic genotype (but only the two-allelic genotype). This and the fact that the haplotype tags the 5-HTTLPR with an imperfect linkage disequilibrium of r2=0.775 may lead to some loss of power. ConclusionsOur results provide further support for an involvement of the 5-HTTLPR in MDD and represent the first example of demonstrating association between MDD and the S-allele of the length polymorphism repeat using common SNP information from SNP-array data.