rs4532

A case-control association study of 1,237 Pakistani subjects (479 with major depression, 222 with bipolar disorder, 146 with schizophrenia, 390 controls) examined 11 dopaminergic system gene variants. Significant risk associations were found for rs1006737 and rs2238056 (CACNA1c) with bipolar disorder (OR=1.14-1.15), while rs10033951 (DRD5), rs2388334 (POU3F2), and the DRD4 120bp VNTR showed protective effects across disorders (OR=0.81-0.86).

Association study of 55 SNPs in 887 Hungarian adults examining genetic predisposition to aggression measured by the Buss-Perry Aggression Questionnaire. The HTR2A rs7322347 intronic variant showed significant association with aggression after Bonferroni correction (p = 0.0007), with carriers of the minor A allele showing lower aggression levels. The DRD4 rs916455 variant also showed nominal significance (p = 0.0275) but did not survive multiple testing correction.

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%).

A pharmacogenetic study of 446 schizophrenic patients (221 males, 225 females) from West Siberia investigating associations between 41 SNPs in dopaminergic genes and antipsychotic-induced hyperprolactinemia. The study found rs1799836 in MAOB gene associated with hyperprolactinemia in males (OR=0.748, p=0.048), and rs40184 and rs3863145 in SLC6A3 gene associated with hyperprolactinemia in the risperidone/paliperidone subgroup (OR=0.341, p=0.021 and OR=0.362, p=0.043, respectively), indicating protective effects.

Case-control study of 382 schizophrenic patients (220 with tardive dyskinesia, 162 without) examining DRD1 gene polymorphisms. SNP rs4532 showed significant association with tardive dyskinesia (P=0.033, OR=2.0 for GG genotype), and haplotype CGC (rs5326-rs4532-rs265975) was also significantly associated with TD (OR=1.4, permutation P=0.027).

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.

This comprehensive review synthesizes genomic and pharmacogenomic research in schizophrenia, discussing over 200 candidate genes associated with psychotic disorders, genetic mechanisms including copy number variants and microRNA alterations, and pharmacogenomic factors affecting antipsychotic efficacy and safety. Key genes covered include dopamine receptors (DRD1-5), dysbindin (DTNBP1), DISC1, neurotrophic factors, and metabolic enzymes such as CYP2D6, CYP3A4, and COMT, with emphasis on genotype-phenotype correlations in antipsychotic response and side effects.

This is a comprehensive literature review of candidate genes and their single nucleotide variants associated with antipsychotic-induced tardive dyskinesia in schizophrenia patients. The review examined genes involved in dopamine system (DRD1, DRD2, DRD3), catecholamine metabolism (COMT), serotonin system (HTR2A, HTR2C), and other pharmacodynamic and pharmacokinetic pathways. Timely identification of genetic variants in these genes could contribute to developing diagnostic tests and selecting safer antipsychotic therapy.

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.

Family-based association study of 2,037 participants examining five DRD1 polymorphisms in relation to nicotine dependence. rs686 and rs4532 showed significant associations with nicotine dependence measures (FTND, HSI, SQ) in African American and pooled samples (P=0.0048-0.035), with rs686 remaining significant after multiple testing correction. Functional studies demonstrated rs686 in the 3' UTR causes differential DRD1 expression (~27% reduction with G allele, P<0.05).

A pharmacogenetic association study of 446 schizophrenia patients from West Siberia examined 41 SNPs in dopamine pathway genes (DRD1, DRD2, DRD3, DRD4, SLC6A3, MAOA, MAOB) for association with antipsychotic-induced hyperprolactinemia (HPRL). rs1799836 in MAOB showed significant protective association with HPRL in men (OR=0.748, p=0.048), while rs40184 (OR=0.341, p=0.021) and rs3863145 (OR=0.362, p=0.043) in SLC6A3 showed protective effects specifically in risperidone/paliperidone-treated 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.

Haplotype-tagging SNP analysis in 364 individuals from 152 ADHD families identified significant associations between commission errors and SNPs in the DRD2 gene (rs2075654, rs1079596) and between reaction time variability and a SNP in the NET gene (rs3785155). These findings suggest that commission errors and reaction time variability are valid ADHD endophenotypes linked to dopaminergic and noradrenergic pathways.

This association study examined 20 polymorphisms from 12 candidate genes in 163 ADHD probands and 129 controls, finding significant associations with two genes: NET1 (rs998424 P=0.009, rs3785157 P=0.002) and DRD1 (rs4532 OR=1.63 P=0.006, rs265981 OR=1.61 P=0.008). The study used both family-based transmission disequilibrium tests and case-control analyses. No significant effects were detected on cognitive, behavioral, or brain MRI measurements.