rs4680

This is a Turkish-language personalized nutrigenetics and epigenetics coaching report for individual Mehmet Efe Yildirim (Report No. 1332, dated 2023-11-21). The report analyzes the individual's genetic polymorphisms related to nutritional metabolism, food sensitivities, detoxification pathways, and other health-related traits, providing personalized dietary and lifestyle recommendations based on cited scientific literature. This is a direct-to-consumer genetic test report, not a peer-reviewed research study.

A candidate gene association study of dementia risk in 2,857 older postmenopausal women from the Women's Health Initiative Memory Study examining 96 SNPs across five genes (APOE/TOMM40, BDNF, COMT, SORL1, KIBRA). The APOE/TOMM40 locus showed the strongest association (rs157582: OR=1.64, p=2.4×10⁻⁸ for probable dementia), with additional significant associations in COMT (rs737865), BDNF (rs1491850), and KIBRA (rs4320284, rs2241368, rs244904). Results support APOE/TOMM40 as a dementia risk locus and extend associations to COMT, BDNF, and KIBRA genes.

Meta-analysis of 20 case-control studies examining the association between COMT gene rs165599 SNP and schizophrenia. Found no statistically significant overall association under four genetic models (OR ranged 0.955-0.985), though sex-specific analysis showed G allele carriers had increased schizophrenia risk in females (OR=1.366, 95% CI=1.094-1.706) compared to AA homozygotes.

Retrospective association study of 162 Brazilian Parkinson's disease patients showing that MAO-B rs1799836 A/AA genotypes and COMT rs4680 L/L genotype are significantly associated with levodopa-induced dyskinesia (OR 2.59, p=0.0139 and OR 5.53, p=0.0009). Male patients carrying the MAO-B G allele had a 2.84-fold increased risk of requiring high-dose levodopa treatment (p=0.04), suggesting sexual dimorphism in dopamine metabolism genes affects PD treatment response.

A prospective pharmacogenetic study of 220 treatment-resistant depression (TRD) patients examined 50 tag SNPs in 14 neuroplasticity and second messenger pathway genes for association with antidepressant response. Key findings included replication of ZNF804A rs7603001 with venlafaxine response (OR=2.51), CREB1 rs2254137 with remission, CHL1 rs2133402 with lower TRD risk, and MAPK1 rs6928 with all phenotypes (p=0.0006 after Bonferroni). Pathway analysis in STAR*D (n=1846) identified protein processing in the endoplasmic reticulum pathway as a potential mechanism of MAPK1 involvement.

A twin study of 1,312 children investigating genetic mediation of endophenotypes in ADHD. Using candidate gene SNPs from dopaminergic, noradrenergic, and serotonergic pathways, the study found the strongest association between rs7984966 in HTR2A and reaction time variability (P=0.007), and rs3785157 in SLC6A2 with commission errors. Mediation analyses revealed that commission errors mediated 38% of the SLC6A2-inattention association, and reaction time variability mediated 44% of the HTR2A-inattention association, suggesting these cognitive measures are intermediate phenotypes on the genetic pathway to ADHD.

This review examines neurogenetic and neuropharmacological correlates of opioid use disorder (OUD) with emphasis on ancestry-specific genetic risk profiles. The paper identifies multiple genes involved in the reward pathway (DRD2, DRD3, DRD4, OPRM1, OPRK1, OPRD1, BDNF, NRXN3, COMT, SLC6A4, KCNC1, KCNG2) and their variants associated with OUD susceptibility and treatment response across different ethnic populations, highlighting critical research disparities where African Americans and Hispanics have been underrepresented in genetic association studies.

Unable to classify: file contains only a single PowerPoint presentation slide showing fMRI neuroimaging results with COMT Val158Met genotype associations in medial prefrontal cortex (mPFC) and cuneus/precuneus regions. No abstract, methods, or complete paper text present.

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 pharmacogenetic study in 61 first-episode schizophrenia patients found that GRM3 rs1468412 TT genotype was associated with worsening spatial working memory performance after antipsychotic treatment (p=0.001, Cohen's d=0.75), while GRM3 rs6465084 AA genotype was associated with improved negative symptoms after treatment (p=0.046). No significant associations were found between COMT Val158Met or DRD2/ANKK1 variants and cognitive or symptom changes.

A case-control study of 830 Korean breast cancer patients and 390 controls evaluating associations between genetic polymorphisms in estrogen receptor genes (ESR1, ESR2) and estrogen-metabolizing enzyme genes (CYP1A1, CYP1B1, COMT) with breast cancer risk. ESR1 rs2881766 (OR=1.40, p=0.02), rs2077647 (OR=1.37, p=0.02), rs926778 (OR=1.56, p≤0.01), and rs2273206 (OR=1.40, p=0.01) increased breast cancer risk, while rs3798377 (OR=0.76, p=0.05) decreased risk in overall patients. Associations varied substantially by age group and tumor subtype, with rs2881766 consistently increasing risk across all age groups except luminal B subtype.

This case-control study (398 AD cases, 149 controls) investigated the COMT Val158Met polymorphism (rs4680 G>A) in a Japanese population and found no direct genetic association with Alzheimer's disease onset. However, a significant association was detected between rs4680 and high alcohol consumption in AD patients (HAC-AD group, OR=0.52 for A allele), with APOE ε4 and COMT G allele exerting synergistic effects (APOE4 OR=2.17, COMT G allele OR=1.92). SPECT imaging revealed hyperperfusion in the right insula of patients with the G/G genotype, suggesting compensatory dopaminergic pathway dysfunction.

This molecular imaging genetics study investigated 52 healthy Caucasian volunteers to determine whether the common COMT gene polymorphism rs4680 (VAL158MET) affects serotonin-1A (5-HT1A) receptor binding. Using PET imaging with [carbonyl-11C]WAY-100635, the researchers found that homozygote GG carriers showed significantly higher 5-HT1A receptor binding potential compared to A carriers (AA+AG) in multiple brain regions including the posterior cingulate cortex (F(2,49)=17.7, p=0.05, FWE corrected), orbitofrontal cortex, anterior cingulate cortex, insula, amygdala, and hippocampus. The effect sizes were large (Cohen's d=1.43 for AA vs. GG), supporting the hypothesis that COMT may modulate serotonergic neurotransmission relevant to mood and anxiety disorders.

This case-control study of 468 schizophrenia patients treated with clozapine (202 with metabolic syndrome, 266 without) examined associations between three COMT gene polymorphisms (rs4633, rs4680, rs4818) and metabolic parameters. The key finding was a significant association between rs4680 (the Val158Met variant) and elevated triglyceride (TG) levels (corrected P=0.024), particularly among female patients (P=0.009), suggesting a potential role for COMT variation in clozapine-associated metabolic syndrome.

A case-control study of 576 fetuses/newborns with neural tube defects (NTDs) and 594 controls in a Chinese population examined MTHFR and COMT gene variants. The MTHFR rs1801133 TT genotype was associated with increased NTD risk (OR=1.37), and a synergistic interaction between COMT rs737865 CC and MTHFR rs1801133 TT genotypes showed over 3-fold increased risk for NTDs (OR=3.02) and anencephaly (OR=3.39), suggesting these variants interact to modulate folate metabolism and increase birth defect susceptibility.

This literature review examines the influence of genetic polymorphisms on obesity development and adaptive responses to physical activity, focusing on five candidate genes: COMT (rs4680, Val158Met), DRD2 (rs1800497 Taq1A and rs1799732), FABP2 (rs1799883, Ala54Thr), FTO (rs9939609, A/T), and UCP1 (rs1800592, A-3826G). The review synthesizes molecular mechanisms, phenotypic associations, and implications for human health and training adaptations, noting that physical activity reduces the FTO genetic effect on obesity risk by 30-80% and that various polymorphisms show differential impacts on body composition and metabolic responses to exercise.

This imaging genetics study examined 94 healthy subjects to investigate the association of rs1006737 in CACNA1C (a bipolar disorder and schizophrenia susceptibility locus) with brain activation and connectivity during working memory tasks. The rs1006737 A (risk) allele was associated with reduced right dorsolateral prefrontal cortex (DLPFC) activation during the 2-back task, contrary to previous findings of increased activation. The study found increased functional connectivity between the right DLPFC and bilateral hippocampal formations in A allele carriers, supporting a fronto-hippocampal dysconnectivity phenotype linked to genetic susceptibility for psychosis.

This study investigated the association between the COMT Val158Met polymorphism (rs4680) and personality traits in 80 healthy female university students. The study found that Val158 homozygotes scored significantly higher on the character dimension cooperativeness compared to Met158 homozygotes (P=0.03), with no differences in other temperament or character scales. The findings support the hypothesis that the Val158 allele is associated with greater cooperativeness, helpfulness, and empathic traits, linking these behavioral characteristics to dopaminergic system function.

This candidate gene association study examined 10 SNPs in addiction-related genes (CNR1, FAAH, DRD2, ANKK1, COMT, OPRM1) in university students and identified the FAAH C385A (rs324420) CC genotype as significantly associated with risky alcohol consumption (p=0.006, OR=2.38). The finding was replicated in an independent sample of 83 participants. Additionally, affective ratings of drug-related pictures were positively correlated with alcohol, tobacco, and cannabis consumption.

High-density SNP mapping of 14 noradrenergic genes in 270 ADHD families (810 individuals from Ireland and Australia) revealed suggestive single-SNP associations but significant haplotype associations in SLC6A2 (5-SNP haplotype: rs36009, rs1800887, rs8049681, rs2242447, rs9930182; χ²=9.39, p=0.019, OR=1.51) and ADRA1B (6-SNP haplotype: rs2030373, rs6884105, rs756275, rs6892282, rs6888306, rs13162302; χ²=7.79, p=0.042, OR=2.74). Notable single-SNP findings included rs8047672 in SLC6A2 (χ²=7.21, p=0.007, OR=2.04) and rs6888306 in ADRA1B (χ²=5.95, p=0.014, OR=1.46), supporting a role of the noradrenergic pathway in ADHD genetic risk.

Association study of 807 male youth examining the COMT Val108/158Met polymorphism (rs4680) and ADHD symptoms. Met/Met genotype was significantly overrepresented in subjects with hyperactive-impulsive and inattentive symptoms (χ² p=0.003), with Met allele frequency 44.6% in controls vs 51-56% in symptomatic groups. Significantly higher symptom scores observed in Met/Met homozygotes compared to Val carriers.

The Acute to Chronic Pain Signatures (A2CPS) is a multicenter prospective observational study protocol designed to identify biomarkers and biosignatures that predict development of chronic postsurgical pain. The study will recruit 3,600 patients undergoing knee arthroplasty or thoracic surgery and collect comprehensive biopsychosocial assessments including genetic variants via the Infinium Global Screening Array (GSA BeadChip with >650,000 markers), brain imaging, quantitative sensory testing, proteomic/metabolomic analyses, and patient-reported outcomes at baseline, 6 weeks, 3 months, and 6 months to identify predictive biomarkers for the transition from acute to chronic pain.

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

This dissertation examined the influence of ovarian steroids on hippocampal memory function and morphology, with Experiment 2 investigating the association between a CYP19A1 SNP (rs700518) predicting estrogen levels and hippocampal gray matter volume in healthy young men (N=161 for structural imaging, N=157 for behavioral testing). The rs700518 polymorphism showed significant associations with posterior hippocampal volume (Cohort A: left Z=3.73 p=.017, right Z=3.76 p=.015; Cohort B: left Z=3.75 p=.016, right Z=4.40 p=.001), where AA genotype carriers (high E2 disposition) had greater hippocampal gray matter than AG/GG carriers (low E2 disposition). However, behavioral memory tasks (emotional memory, spatial learning, verbal source memory) showed no significant genotype differences.

A candidate gene association study in 100 Russian vitiligo patients and 100 controls identified a strong novel association between GSTP1 rs1138272 (Ala114Val, OR=13.03, Bonferroni-adjusted P=0.0015) and vitiligo susceptibility. Cumulative analysis of multiple xenobiotic metabolizing genes showed that carrying higher numbers of risk alleles was associated with increased vitiligo risk (9-16 vs 3-8 alleles: OR=2.79, P=0.00063), supporting a polygenic model for vitiligo involving detoxification pathway genes.

This fMRI study investigated the replication of rs1344706 genotype effects on brain functional connectivity in 94 healthy subjects. While previous studies reported decreased interhemispheric prefrontal cortex connectivity and increased fronto-hippocampal connectivity associated with rs1344706 risk alleles, this independent replication found partial support: no significant interhemispheric DLPFC coupling reduction, but confirmed increased functional connectivity between right DLPFC and hippocampal formations with higher risk allele count (exploratory analysis, P<0.05 uncorrected).

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.

Two-stage replication study of 9 SNPs in 8 genes previously associated with breast cancer survival in 6,307 Chinese women (Stage 1: 1,115 cases, Stage 2: 5,192 cases). MMP7 rs11225297 and MMP8 rs11225395 showed consistent associations with overall survival, with rare alleles conferring 20-40% improved survival (HR 0.4-0.6 and 0.6 for TT genotypes respectively, p<0.001).

This cross-sectional association study examined how age modulates the effects of the COMT Val158Met polymorphism (rs4680) on delay discounting behavior. Among 142 participants (18-40 years), met-allele carriers showed decreased delay discounting with age while val/val homozygotes showed increased delay discounting, representing a significant age-by-genotype interaction (F(2,128)=5.15, p=0.007). The findings reconcile conflicting literature between adolescent and adult studies and support a U-shaped model of dopamine regulation.

Large candidate gene association study of fibromyalgia identifying genetic risk factors across 350 genes involved in nociception, inflammation, and mood. Discovery phase (496 FM patients, 348 controls) found significant associations for GABRB3 (rs4906902, p=3.65×10⁻⁶, OR=0.46), TAAR1 (rs8192619, p=1.11×10⁻⁵, OR=3.8), and GBP1 (rs7911, p=1.06×10⁻⁴, OR=1.7). Replication phase (1004 FM cases, 3725 controls) confirmed association for TAAR1, RGS4, CNR1, and GRIA4 genes, suggesting multiple biological pathways underlying fibromyalgia susceptibility.

A randomized, double-blind, placebo-controlled crossover study in 50 subjects (25 AA and 25 GG for COMT rs4680) examined the impact of green tea extract on vascular function and blood pressure. The COMT Val158Met (rs4680) polymorphism modulated the acute vascular response to green tea, with the low-activity AA genotype showing significant attenuation of reflection index changes (p=0.014 for genotype×treatment interaction, p=0.029 within AA group). The GG genotype showed greater urinary 4'-O-methyl epigallocatechin excretion (p=0.049), suggesting differential catechin metabolism by COMT genotype.

This review examines polymorphisms in six genes (SCN9A, KCNS1, GCH1, COMT, OPRM1, OPRK1) involved in nociception and their associations with chronic post-surgical pain (CPSP). Key findings include rs4680 in COMT associated with higher pain risk (OR 3.42 in knee replacement patients), rs734784 in KCNS1 explaining ~5% of pain variance in lumbar discectomy patients, and rs6746030 in SCN9A conferring increased pain sensitivity. The paper reviews conflicting evidence across multiple surgical populations and discusses potential clinical applications of genetic testing for CPSP risk stratification.

This functional neuroimaging study examined how the COMT Val158Met polymorphism (rs4680) modulates neural activity underlying inhibitory control in 42 healthy participants (21 Met158/Met158 homozygotes, 21 Val158/Val158 homozygotes) using magnetoencephalography during a Go/NoGo task. Met158 allele carriers (high dopamine) showed a transient increase in beta power (~100 ms) during early motor preparation suggestive of a motor 'pause', while Val158 homozygotes (low dopamine) exhibited greater beta desynchronization indicative of higher response readiness. These neural differences correlated with personality traits and behavioral disinhibition (extraversion, impulsivity) despite no differences in task performance.

This systematic review and validation study examined psychosis-associated SNPs and their effects on brain volumetry in 113 subjects (schizophrenia, bipolar disorder, at-risk mental state, and healthy controls). Of 25 studies identified in the systematic review implicating 7 SNPs in 5 genes, the authors tested these variants using voxel-based morphometry. They found FWER-corrected associations for CACNA1C rs769087-A with larger bilateral hippocampus and thalamus white matter (p = 0.026 and p = 0.036) and with larger superior frontal gyrus volume. Higher replication concordance was found for CACNA1C, ZNF804A, and BDNF variants, supporting their involvement in psychosis and brain structure.

Case-control study of 604 Han Chinese examining associations between two COMT gene polymorphisms (rs740603 and rs4818) and schizophrenia. Found no significant association with schizophrenia susceptibility, but rs740603 and the rs740603(G)-rs4818(G) haplotype were associated with negative symptoms severity, particularly in females (p=0.025 for rs740603; p=0.021 for haplotype in females).

This population-based study of 3,904 subjects examined the interaction between COMT and TXNRD2 SNPs and temporomandibular disorder (TMD) pain, modified by depressive symptoms. Six SNPs from the first COMT/TXNRD2 haploblock showed significant interactions with depressive symptoms (smallest p-value: 2.7 × 10^-10), with opposite SNP effects between depressed and non-depressed individuals. In non-depressed subjects, rs5993882 (COMT) was most associated with TMD pain, while in depressed subjects, rs1544325 (COMT) and TXNRD2 SNPs were preferentially associated. The findings indicate that COMT polymorphisms affect pain perception through a mechanism significantly moderated by depressive symptoms.

This candidate gene association study examined 14 SNPs in ADRB2 and COMT genes in 1,004 Western Australian adolescents (age 17) to identify genetic variants associated with chronic musculoskeletal complaints. Of the SNPs tested, only rs2053044 in ADRB2 (recessive model) showed association with chronic disabling neck and low back pain (OR = 2.49; 95% CI = 1.25-4.98; p = 0.01) and pain in 3-4 body areas (OR = 1.86; 95% CI = 1.13-3.06; p = 0.02). The findings suggest that genetic variants in ADRB2 may be involved in regulating chronic musculoskeletal pain in adolescents.

Case-control study of 112 Brazilian fibromyalgia patients and 110 healthy controls examining COMT gene SNPs rs4680 and rs4818. The homozygous mutant genotype AA of rs4680 was present in 77.67% of patients vs 28.18% of controls (FIQ score 87.92 vs 15.56). The CC genotype of rs4818 was found in 73.21% of patients vs 39.09% of controls (FIQ score 86.14 vs 13.13). Both SNPs showed significant association with fibromyalgia and elevated pain sensitivity (p < 0.001).

This case-control and family-based study evaluated 64 SNPs in 34 genes for associations with spina bifida in 558 Irish case-families and 994 controls. Spina bifida was significantly associated with LEPR rs1805134 (GRR: 1.5, P = 0.0264) and COMT rs737865 (GRR: 1.4, P = 0.0206), with additional confirmations of previous findings in MTHFR 677C>T and other genes, suggesting roles for leptin signaling and methylation pathways in neural tube defect pathogenesis.

An Italian preliminary study of 32 female patients with eating disorders (25 anorexia nervosa, 5 bulimia nervosa, 2 binge eating disorder) investigated the association between dopaminergic system polymorphisms (DRD2, DRD4, COMT, DAT) and body image disturbance. While high body image disturbance was confirmed in patients, the study found no statistically significant differences in polymorphism distributions between diagnostic groups. A significant association was found only for the DAT 10R/10R genotype (χ²=21.57; p=0.006 for DRD4) with increased body dissatisfaction scores in specific body regions, but overall the preliminary results did not support the hypothesis of shared Reward Deficiency Syndrome polymorphisms with addiction disorders.

Case-control study investigating five estrogen metabolism gene polymorphisms in two populations of African ancestry (498 Guadeloupean cases/565 controls and 162 Congolese cases/144 controls). The COMT rs4680 AA genotype was inversely associated with prostate cancer risk (OR: 0.53, 95% CI: 0.32-0.88 in Afro-Caribbean; OR: 0.26, 95% CI: 0.08-0.83 in native African populations), with stronger associations in low-grade cancers and localized stage disease.

This review examines the TCF4 gene's role in schizophrenia genetics, particularly the schizophrenia risk variant rs9960767 (C allele). In a sample of 401 schizophrenia patients, the TCF4 C-allele was associated with better recognition memory in verbal learning tests, contrary to expectations. The C-allele of rs9960767 was also associated with reduced sensorimotor gating (prepulse inhibition), suggesting TCF4 influences early information processing deficits in schizophrenia, though it did not modulate antipsychotic drug response.

This association study examines COMT polymorphisms and cocaine-induced paranoia (CIP) in European-American and African-American populations. The nonsynonymous Val158Met variant (rs4680) and three additional SNPs (rs933271, rs5993883, rs740603) were identified as potentially functional. Family-based and case-control analyses revealed significant haplotype associations with CIP, particularly haplotype A-A-T in both European-American families and unrelated African-American individuals, supporting COMT's role in dopamine/norepinephrine metabolism affecting cocaine-induced psychiatric symptoms.

This is a comprehensive book chapter reviewing cannabinoids and the brain from an MIT Press publication (2017) by Linda Parker. It covers the endocannabinoid system, THC and CBD pharmacology, and effects on brain functions including psychosis. The psychosis chapter discusses genetic factors modulating cannabis-induced psychotic risk, including COMT Val158Met polymorphism showing 10-fold increased risk for Val/Val carriers, AKT1 rs2494732 showing 2-fold increased psychosis risk with C/C genotype, and other candidate genes DAT1, BDNF, and CNR1.

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 pilot association study examining single nucleotide variants rs6280 in DRD3 and rs9652490 in LINGO1 genes and their association with levodopa-induced dyskinesias (drug dyskinesia) in Parkinson's disease patients from Yakutia, Russia. The study of 47 PD patients (7 with dyskinesias, 40 without) found no statistically significant association between either SNV and drug dyskinesia development (p > 0.05), though longer levodopa therapy duration and higher equivalent daily levodopa doses were significantly associated with dyskinesia risk.

This candidate gene association study examined 95 treatment-refractory schizophrenia patients genotyped for seven GRM3 markers. Two SNPs (rs1989796 and rs1476455) at the 3' end of the gene were significantly associated with global psychosis symptoms measured by BPRS total scores (rs1476455: CC genotype 55.1±10.4 vs A-carriers 48.3±9.2, F=7.6, p=0.0071; rs1989796: CC genotype 50.1±5.7 vs T-carriers 55.8±10.5, F=7.1, p=0.0091), but not with negative symptoms.

This case-control study identified biallelic combinations of genetic variants associated with vasovagal syncope using Bayesian statistical analysis in 175 VVS patients and 200 controls. Eleven pairwise combinations of SNPs from neurohumoral regulation genes and the 2q32.1 locus were identified, with five showing significant epistatic interactions. Key associations included COMT*G with OR=2.04 (p=0.0015) and COMT*G + ADORA2A*C/C with OR=2.78 (p<0.001), suggesting a common genetic background between syncope and cardiovascular pathology.

A comprehensive review book examining the endocannabinoid system and cannabinoids in the brain, covering their effects on emotional regulation, psychosis, learning, memory, reward, appetite, pain, epilepsy, and neurodegenerative disorders. The book discusses genetic variations in COMT (Val158Met), AKT1 (rs2494732), FAAH, BDNF (Val66Met), CNR1, GPR55, and CYP2C9 that modulate cannabis effects on psychosis, cognition, and neurological function.

This Hungarian dissertation examined psychogenetic endophenotypes in healthy young adults (N~1800+), investigating associations between dopaminergic and serotonergic genetic polymorphisms and psychological traits including impulsivity, mood dimensions, flow susceptibility, hypnotizability, and cognitive performance. Key findings included significant associations between DRD4 VNTR 7-repeat allele and lower impulsivity (p=0.006), COMT Val/Met (rs4680) and impulse control (p=0.047), HTR1B 1997 AG (rs13212041) and impulsivity (p=0.003-0.004), GDNF variants and anxiety, and notably, a population frequency increase in DRD4 7-repeat allele carriers with advancing age suggesting possible survival advantage.