rs6311

This international doctoral thesis examined gene-physical activity interactions in fibromyalgia through six studies analyzing 64 SNPs across 34 candidate genes in Spanish women. The case-control study (314 fibromyalgia cases vs. 112 controls) identified associations of rs841 (GCH1), rs1799971 (OPRM1), and rs2097903 (COMT) with fibromyalgia susceptibility (p=0.04, p=0.02, and p=0.04 respectively). Cross-sectional studies (n=274-276 fibromyalgia patients) found that SCN9A rs4453709 and other genetic polymorphisms interacted with physical activity to influence pain, fatigue, and resilience outcomes.

This PhD thesis presents four genetic and epigenetic studies investigating risk factors for suicidal behavior in schizophrenia. Study 1 (n=241 schizophrenia patients) found that only rs2661319 in RGS4 was significantly associated with suicide attempt (p=0.002) among 384 SNPs tested, with RGS4 showing lower potential methylation in attempters (55% vs 65%, p=0.005). Studies 2-4 examined HTR2A and HTR1B methylation and expression in smaller samples (n=47-80) but found no strong evidence that genetic or epigenetic factors significantly predict suicidal behavior. Overall conclusion: no robust genetic or epigenetic predictors of suicide were identified in this schizophrenia population.

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.

PhD thesis examining genetic and epigenetic factors associated with suicidal behavior in schizophrenia patients. Four studies tested associations between DNA variants (384 SNPs in candidate genes) and suicide attempt/completion, including analysis of CpG methylation sites. Key finding: rs2661319 in RGS4 was significantly associated with suicide attempt (p=0.002) with differential potential methylation levels (55% in attempters vs 65% in non-attempters, p=0.005). However, overall study found limited evidence that genetic or epigenetic factors significantly influence suicide risk in schizophrenia.

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 comprehensive review examines the pharmacogenetics of antipsychotic drug treatment, synthesizing evidence on how genetic variations influence both treatment efficacy and adverse effects. Key findings show dopamine receptor genes (DRD2, DRD3) predominantly associated with positive symptom response, while serotonin genes (HTR1A, HTR2A, HTR2C) associate with negative symptom improvement. For weight gain, the HTR2C promoter polymorphism (-759 C/T) shows strong protective effects (relative risk 3.45) in risperidone/olanzapine treatment. Tardive dyskinesia associations involve multiple genes including DRD2, DRD3, HTR2A, HTR2C, and SOD2, though GWAS findings often diverge from candidate gene results.

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 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.

Meta-analytic review of candidate gene studies for childhood ADHD examining 19 genes. Significant associations identified for DAT1 (3' UTR VNTR: OR=1.12, p=0.028; rs27072: OR=1.20, p=0.006), DRD4 (exon 3 VNTR: OR=1.33, p=0.00007; rs1800955: OR=1.21, p=0.007), DRD5, 5HTT, HTR1B (rs6296: OR=1.11, p=0.010), and SNAP25 (rs3746544: OR=1.15, p=0.030).

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.

This study investigated whether HTR2A A-1438G/T102C polymorphisms (rs6311/rs6313) predict aripiprazole treatment response in 128 Han Chinese schizophrenia patients. The GG/CC genotype group predicted poor negative symptom response (PANSS negative score 3.93 points higher in GG/CC vs. AA/TT, P=0.007), with clinical factors like medication dosage and age also significantly influencing treatment outcomes.

This review of molecular genetic studies of ADHD in Han Chinese populations summarizes candidate gene studies across dopaminergic, noradrenergic, serotonergic, and enzymatic systems, along with the first GWAS in Chinese ADHD cases (n=1040) and controls (n=963). While no single gene has been definitively identified, significant associations include DRD4 7-repeat allele (OR=1.70, 95% CI 1.20-2.40, p=0.003 in males), DBH rs2519152, and various polymorphisms in COMT, NET1, and serotonin genes, though results remain inconsistent across studies.

Case-control study investigating associations between three SNP polymorphisms (COMT rs4680, 5-HT2A rs6313, rs6311) and fibromyalgia syndrome susceptibility in 80 FMS patients and 91 controls. No significant differences were observed in allele or genotype frequencies between patients and controls for any of the three polymorphisms (all P > 0.05), suggesting these variants are not susceptibility factors for FMS.

A comprehensive review of major autism spectrum disorder (ASD) bio-collections and their research findings from 2001-2016, summarizing 263 studies. The review covers mapping of ASD candidate genes, frequency of gene mutations in clinical subgroups, molecular pathways including synapses and chromatin remodeling, and emerging use of induced pluripotent stem cells for modeling ASD. Key genes identified include MECP2, PTEN, EN2, RELN, RORA, MET, SCN1A, and others, with evidence for de novo and inherited copy number variants in 10% of sporadic ASD cases.

PhD thesis investigating genome-wide transcriptional and methylomic consequences of a balanced t(1;11) chromosomal translocation linked to schizophrenia, bipolar disorder, and major depression. DNA methylation profiling in 41 family members identified differential methylation at translocation breakpoint regions (chromosomes 1 and 11) and genes related to psychiatric disorders and neurodevelopment. Gene expression analysis in lymphoblastoid cells (13 family members) and iPSC-derived neurons (6 individuals) identified SORL1 as a candidate gene, with follow-up functional analysis in Disc1 L100P mouse model and epistasis studies in human GWAS data.

This literature review synthesizes findings on oxytocin (OXT) and vasopressin (AVP) receptor gene polymorphisms and their associations with social behaviors and psychiatric traits including autism, depression, schizophrenia, and stress responses. Key polymorphisms include rs53576 and rs2254298 in OXTR, with varying effects on empathy, prosocial behavior, and psychiatric symptomatology depending on genetic background and environmental factors.

A case-control study of 51 children with obsessive-compulsive disorder (OCD) and 51 healthy controls found that serum BDNF and GSK-3β levels were statistically significantly higher in the OCD group compared to controls. No significant differences were detected in IL-6, hs-CRP, or β-catenin levels. The study suggests that BDNF and GSK-3β may serve as neuroinflammatory markers in childhood OCD.

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.

A case-control study (N=99: 49 patients with major depressive disorder, 50 controls) conducted in Mexican mestizo population analyzing 8 genetic variants in serotonin and dopamine receptors (HTR1A rs6295, HTR2A rs6311/rs6313/rs6314, HTR6 rs1805054, DRD2 rs1801028/rs1800497, DRD3 rs6280) using PCR-RFLP genotyping. The study characterized genotype and allele frequencies in depressed patients versus healthy controls and evaluated associations with antidepressant treatment response using Hamilton Depression Scale.

Family-based association study in 42 Antioquia families examining serotonergic gene variants and autism. Found significant associations with SLC6A4 variants rs4583306 (OR=2.6, p=0.004) and rs2066713 (OR=2.2, p=0.03), and evidence of epistasis between SLC6A4 and HTR2A (p<0.001) in autism etiology. The haplotype 5HTTLPR-rs4583306 (S-G) showed tripled autism risk (OR=3.4, p=0.01).

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.

This doctoral thesis conducted multiple candidate gene association studies in 274-426 southern Spanish women with fibromyalgia to investigate gene-physical activity/sedentary behavior interactions with pain, fatigue, and resilience. Study III identified rs841 (GCH1) GG genotype (OR=0.61, p=0.04) and rs2097903 (COMT) AT/TT genotypes (OR=1.66, p=0.04) associated with fibromyalgia susceptibility, and confirmed rs1799971 (OPRM1) GG genotype (OR=0.58, p=0.02) confers genetic risk. Study IV found rs6311/rs6313 (HTR2A) polymorphisms individually associated with algometer pain score, and gene-sedentary behavior interactions involving rs4680/rs165599 (COMT), rs1383914 (ADRA1A), rs12994338/rs4453709 (SCN9A), and rs6860 (CHMP1A) significantly associated with pain outcomes. SCN9A emerged as most robust gene for fibromyalgia phenotype.