rs7305115

This gene-environment interaction study examined 4,504 Caucasian subjects from two independent cohorts (SHIP-LEGEND and SHIP-TREND-0) to assess how variants in serotonergic pathway genes TPH2 (rs7305115) and 5-HTTLPR moderate depression risk after childhood abuse. The three-way interaction between abuse, TPH2 GG genotype, and 5-HTTLPR SS genotype showed significant association with depression severity (p=0.023), with GG/SS carriers exposed to abuse displaying mean BDI-II scores of 15.0 compared to 6.8 in AA carriers, supporting the serotonin deficiency hypothesis in depression.

This case-control study examined associations between TPH2 gene polymorphisms (rs7305115 and rs4290270) and Kawasaki disease with coronary artery lesions (CALs) in 101 Korean children versus 256 controls. While the SNPs showed no association with KD susceptibility itself, both SNPs demonstrated statistically significant associations with CAL development: rs7305115 AA genotype (OR=5.69, p=0.0004) and rs4290270 AA genotype (OR=7.98, p<0.0001) were associated with increased CAL risk in KD patients.

Literature review of 77 publications examining the effects of genes COMT, MAO-A, MAO-B, DAT, DRD2, VMAT2, TPH2, and SNCA on Parkinson's disease neuropsychiatric symptoms and therapy response. Key polymorphisms include rs1800497 (DRD2) associated with impulse control disorders, rs6269/rs4633/rs4818/rs4680 (COMT) with cognitive decline, and rs1352250/rs6582078 (TPH2) with impulse control. The review identifies genetic predictors for early complications (cognitive decline, depression, psychosis, impulse control disorders) and therapy optimization, relevant for patient selection for deep brain stimulation.

This dissertation investigated the genetic basis of violent criminal behavior, antisocial personality disorder (ASPD), and broader antisocial behavior through GWAS and meta-analyses in Finnish and international populations. Study I identified an intronic CDH13 variant (rs11649622, OR=2.7, p=4.19×10⁻⁶) associated with extremely violent offending, replicated in homicide offenders (p=5.3×10⁻⁷, OR=2.17). Study II revealed the first genome-wide significant association between LINC00951 variant rs4714329 (OR=1.59, p=1.6×10⁻⁹) and ASPD. Study III meta-analysis of 16,400 individuals found no genome-wide significant associations with broader antisocial behavior, though polygenic risk scores explained ~5% of phenotypic variance.

This literature review compares genetic and non-genetic contributions of serotonin to suicide risk. The paper examines polymorphisms in serotonin-related genes (TPH, SLC6A4/5-HTT, HTR1A, HTR2A) and non-genetic factors including cerebrospinal fluid 5-HIAA levels and serotonin receptor binding abnormalities. Key findings indicate that reduced serotonin transporter expression (linked to 5-HTTLPR short allele), TPH polymorphisms, and HTR2A variants are associated with increased suicide vulnerability, though results are often inconsistent and require larger-scale studies.

This review article systematically examines the genetic and non-genetic contributions of serotonin to suicide risk. Key findings include associations between suicide and polymorphisms in serotonin pathway genes including TPH (A779C, A218C), 5-HTT/SLC6A4 (5-HTTLPR), HTR1A (C-1018G), and HTR2A (T102C, A-1438G, his452tyr), though findings are inconsistent across studies. The review also discusses non-genetic factors such as reduced cerebrospinal fluid 5-HIAA levels and abnormal serotonin receptor densities in postmortem brains of suicide victims.