rs1176713

This association study examined 3,564 subjects from the SAGE dataset (2,428 European-American, 1,136 African-American) to determine associations between 88 variants in HTR3A, HTR3B, and SLC6A4 genes and alcohol, cocaine, and nicotine dependence. Individual SNP analysis found rs2066713 in SLC6A4 significantly associated with FTND in African-Americans (beta = -1.39, P = 1.6E-04). Haplotype analysis identified major haplotypes in HTR3B and HTR3A significantly associated with alcohol dependence and FTND. GMDR interaction analysis revealed significant SNP-by-SNP interactions within these three genes affecting multiple addictive phenotypes.

This case-control association study examined 22 SNPs in HTR3A, HTR3B, and SLC6A4 genes in relation to alcohol dependence in 500 cases and 280 controls of European descent. Low-frequency variants rs33940208 (HTR3A) and rs2276305 (HTR3B) showed protective effects (OR=0.212, P=0.004 and OR=0.261, P=0.016 respectively). Gene-by-gene interaction analyses revealed significant interactive effects among SLC6A4, HTR3A, and HTR3B variants on alcohol dependence risk (OR=2.71-3.095, P<0.001-2×10⁻⁴). Findings were replicated in 6,699 samples from the OZ-ALC-GWAS study.

In 101 treatment-resistant schizophrenia patients, the T allele of HTR3A rs1062613 and G allele of rs2276302 were significantly associated with good response to clozapine (p=0.02), with odds ratios of 9.00 and 5.99 respectively. However, these associations were highly dependent on outcome definition, explaining only 13.8% of clozapine response variability, while combined clinical and genetic predictors explained 38% of variability.

This comprehensive review examines the genomics of schizophrenia and pharmacogenomics of antipsychotic drugs, synthesizing evidence on over 200 genes associated with psychotic disorders. The authors discuss five categories of genes relevant to antipsychotic response: disease-associated genes, mechanism-of-action genes, drug metabolism genes (particularly CYP2D6, CYP2C19, CYP2C9, CYP3A4), drug transporter genes, and pleiotropic genes. The review details pharmacogenomic profiles of 20+ antipsychotic drugs and demonstrates significant ethnic and interindividual variation in drug metabolism phenotypes, with examples including CYP2D6 extensive metabolizers (55.71% of population), intermediate metabolizers (34.7%), poor metabolizers (2.28%), and ultra-rapid metabolizers (7.31%).

This systematic review of 98 studies examined biological predictors of clozapine response in treatment-resistant schizophrenia patients. Of 379 different gene variants investigated across 70 genetic studies, only three variants (DRD3 Ser9Gly rs6280, HTR2A His452Tyr, and GNB3 C825T) achieved independent replication. Non-genetic predictors included higher prefrontal cortical volumes and lower HVA:5-HIAA ratio in cerebrospinal fluid.

A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.