Single nucleotide polymorphism and haplotype analysis of a novel tryptophan hydroxylase Isoform (TPH2) gene in suicide victims

Genetic architecture of the human tryptophan hydroxylase 2 Gene: existence of neural isoforms and relevance for major depression

“…These results provide evidence for association of TPH2 with major depression and/or suicide, since the majority of our cases had major depression and had committed suicide, and therefore support previous reports of associations of a TPH2 variant (rs1386494) with both depression 19 and suicide 20 …”

“…Although numerous haplotype block definitions are possible, we adopted the more conservative four-gamete test, 33 yielding a total of nine blocks ranging from 88 to 15 335 bp in length. The associations with major depression reported previously 19,20 and in the present study, fall entirely within the second block. Within these haplotype blocks, spanning 44 SNPs, we identified 15 tag-SNPs (Table 3).…”

“…This is because a more critical evaluation indicates that the association with rs1386493 might be spurious. Specifically, the direction of association for marker rs1386493 in this study as well as previously reported studies 19,20 indicates the potential presence of a common risk allele, as observed in the pattern of allelic and genotypic frequencies in cases versus controls, where the major allele is more common in cases than controls. This trend is observed for both major depression and suicide (for example, 0.93/0.79 corresponding to cases/controls within the depression clinical model).…”

“…The first is locus rs1386493 that is 2636 bp downstream from rs1386494, the locus reported previously to be associated with depression and suicide. 19,20 The second is the novel variant g.22879A > G discovered in our present study. The strongest evidence for association was observed with the major depression clinical model (rs1386493-P = 0.001 and g.22879A > G-P = 0.05), that remained statistically significant after adjustment for multiple models and markers tested (global empirical P = 0.01).…”

“…Recent studies report associations of TPH2 with major depression and with suicide, involving single nucleotide polymorphisms (SNPs) in intron 5 and exon 11. 12,13,19,20 Thus, while we explored the coding portion of the TPH2 gene and sections of each intron, we focused our analyses on the SNPs that lie in these two regions in an effort to replicate the previously reported positive findings in our dataset. In addition, we report on the first systematic examination of the TPH2 gene variants covering both the coding and non-coding regions and transcript variants in human brain.…”