SNPs in the NTRK2 gene are associated with depressive disorder

Background: Recent work has raised the hypothesis that regulation of neurotrophins may be important for the outcome of antidepressant treatment. Whereas many case-control association studies on psychiatric phenotypes focused mainly on the functional Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene obtaining conflicting results, almost no human genetic studies have been reported on the tyrosine kinase receptor 2 (NTRK2) gene, the high-affinity receptor of BDNF. Objective: To investigate a possible association between NTRK2 and depressive disorder, we systematically genotyped 59 SNPs throughout the NTRK2 gene. DESIGN: We performed a case-control study in an exploration (Expl) sample consisting of recurrent unipolar depressive patients and healthy controls (N=850). Nominally significant associated SNPs of the Expl sample were assessed in a second independent case-control sample (N=1000). Results: We did not find case-control associations that withstood correction for multiple testing over all 59 SNPs in the Expl sample. However, out of totally four uncorrelated SNPs which were nominally significant (p<0.05) in the Expl sample and for which replication was tempted, one of these SNPs, located in the promotor proximal intron 4, reached significance in the replication and combined sample. Another two SNPs were significant in the combinded sample. Conclusion: Our results suggest evidence that NTRK2 may confer susceptibility for depressive disorder.