rs878567

Meta-analysis of 15 studies (4,297 patients, 5,435 controls) found that the serotonin 1A receptor gene (HTR1A) SNPs rs6295 (C-1019G) and rs878567 are significantly associated with mood disorders and major depressive disorder. The rs6295 G allele was protective against mood disorders (OR = 0.87, 95% CI 0.79-0.96, P = 0.007 in allele model), with stronger effects in Asian populations (OR = 0.81, P = 0.0007). rs878567 also showed protective association with mood disorders (OR = 0.83, P = 0.0002).

Case-control association study investigating 42 SNPs in 10 genes in 221 Korean schizophrenia inpatients and 170 healthy controls. The 5HTR1A variant rs10042486 showed significant association with schizophrenia (χ² = 11.32, p = 0.003) and clinical improvement on PANSS scores; subjects with TT genotype showed greater improvement than CC/CT carriers (F = 178.77, p = 0.002 for PANSS total; p < 0.001 for positive and negative subscales). No significant associations were found for the other 41 SNPs.

This review chapter synthesizes genetic research on suicidal behavior, covering family, twin, and adoption studies demonstrating ~45% heritability. It highlights key serotonergic genes (TPH1, TPH2, 5-HTT, 5HTR1A, 5HTR2A) associated with suicide risk, dopaminergic pathway genes (DRD2, COMT Val158Met showing increased risk), BDNF (reduced levels in suicide victims), and genome-wide linkage studies identifying suicide risk loci on chromosomes 2p, 5q, 6q, 8p, 11q, and Xq. The review concludes that serotonergic candidates represent the most credible evidence for genetic susceptibility to suicide.

This two-stage case-control association study examined four SNPs spanning the HTR1A gene (serotonin 1A receptor) in 589 cases and 539 controls selected for extreme genetic risk of depression and anxiety disorders. Although rs1364043 showed nominally significant association in stage 1 (P<0.1), this failed to replicate in stage 2, and multi-marker haplotypes including the previously implicated C(-1019)G promoter polymorphism (rs6295) showed no consistent associations. The findings suggest HTR1A genetic variation alone is unlikely to contribute substantially to genetic susceptibility to depressive and anxiety-related phenotypes.

This association study examined epistatic interactions among seven serotonin pathway genes in autism etiology using 186 autistic families and 181 controls. The authors found a significant main effect of HTR5A rs1800883 (P = 0.0088), and identified a significant three-locus epistatic interaction between SLC6A4 intron 2 VNTR and ITGB3 rs5918 with additive HTR5A rs6320 effects (P < 0.001) associated with autism risk. Additionally, ITGB3 haplotypes showed association with platelet serotonin levels (P = 0.0163), supporting a common genetic mechanism linking gene interactions to both autism susceptibility and hyperserotonemia.