rs11030099

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.

This population-based case-control study examined the association between BDNF rs6265 polymorphism and smoking cessation behavior in 20,584 Taiwanese adults from the Taiwan Biobank. Contrary to previous studies suggesting association between rs6265 and smoking behavior, this study found no significant association between the polymorphism (TT, TC, CC genotypes) and smoking cessation (p = 0.8753). Instead, sociodemographic and lifestyle factors (age, education, marital status, drinking, exercise, BMI) were significant predictors of smoking cessation, with males (OR 0.750), drinkers (OR 0.707), and underweight individuals (OR 0.597) less likely to quit smoking.

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.

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 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.

A case-control study of 248 asthmatic children and 249 healthy controls examining the BDNF Val66Met polymorphism (rs6265). The Met/Met variant was associated with increased asthma risk (OR=4.17, p=0.018), while the Val/Met genotype was protective (OR=0.69, p=0.045), especially in girls (OR=0.34, p=0.001). These findings suggest BDNF gene variations contribute to asthma susceptibility in children.

This candidate gene association study examined 82 participants (38 with major depressive disorder, 44 healthy controls) to investigate how the BDNF Val66Met polymorphism (rs6265) interacts with childhood adversity to influence hippocampal subfield volumes. Patients with MDD had significantly smaller CA4/DG and CA2/3 volumes compared to healthy controls. Critically, Met-allele carriers showed a significant interaction with childhood adversity: Met carriers with childhood adversity had smaller CA4/DG and CA2/3 volumes, while Met carriers without adversity had larger volumes than Val/Val homozygotes.

Case-control study in 709 Han Chinese individuals (375 schizophrenia patients, 334 controls) examining BDNF gene polymorphisms. While no significant differences were found for single-locus analysis of rs6265 (Val66Met), rs12273539, and rs10835210, the haplotype ATC of rs6265-rs12273539-rs10835210 was significantly more frequent in patients than controls (P=0.027), and the ACA haplotype was significantly associated with negative symptom scores on the PANSS (χ²=5.789, P=0.016), suggesting BDNF gene variants may contribute to schizophrenia susceptibility and negative symptoms in Chinese populations.

This comprehensive literature review examines the role of single-nucleotide polymorphisms (SNPs) and genetic variants in dystonia susceptibility, reviewing 43 published studies (2001-2017) across 29 genes. Key findings include associations of TOR1A variants (rs1182, rs1801968, rs35153737) with focal dystonia, BDNF rs6265 (Val66Met) with cervical dystonia and blepharospasm, and preliminary GWAS-identified variants in ARSG (rs11655081, rs61999318) and NALCN with dystonia risk. The review concludes that genetic factors confer dystonia susceptibility through multiple pathways, though many associations require validation in larger cohorts.

This genome-wide association study identified rs6265 (Val66Met) in the BDNF gene as a phosSNP (phosphorylation-related SNP) associated with bone mineral density (BMD) in three independent populations (~5,000 subjects total). Individuals carrying the AA genotype had significantly lower hip BMD than GA/GG carriers. Functional studies demonstrated that rs6265 regulates BDNF protein phosphorylation at residue T62 and affects osteoblast differentiation through modulation of genes OPN, BMP2, and ALP.

Meta-analysis of 28 studies (range 38-7,173 participants) found no significant association between BDNF genetic variants and major depressive disorder. Val66Met (rs6265) showed OR=0.96 (95% CI: 0.89-1.05; P=0.402), and gene-based analysis of 17 total BDNF SNPs indicated no cumulative association with MDD (all P>0.21).

This review examines how the BDNF val66met polymorphism influences PTSD susceptibility and treatment response through its effects on hippocampal integrity and spatial processing. The paper proposes that patients carrying the met allele have reduced hippocampal volume and plasticity, and may show poorer response to trauma-focused therapies that rely on spatial contextualization. The authors argue that genetic analysis of BDNF genotypes could predict PTSD treatment success and improve clinical referral pathways.

A Master's thesis investigating the role of reelin protein in depression using a rat corticosterone model. The study demonstrates that chronic and intermittent corticosterone treatment produces depression-like behavior and downregulates reelin-positive cells in the hippocampal dentate gyrus, with a significant negative correlation between reelin expression and depressive-like behavior (r = -0.362, p = 0.001). Peripheral reelin injections reversed CORT-induced depression-like behavior and restored endogenous reelin levels, suggesting reelin has antidepressant or neuroprotective effects.

Meta-analysis of five case-control studies (523 geriatric depression cases, 1,220 controls) found that BDNF Val66Met Met allele carriers had significantly increased risk for geriatric depression (P=0.004, OR=1.48, 95% CI=1.13-1.93). The Met allele, associated with reduced BDNF activity and altered hippocampal function, appears to confer greater depression risk in elderly populations than in younger adults.

This prospective study examined the association between BDNF Val66Met gene polymorphism (rs6265) and antidepressant response in 57 Han Chinese patients with first-episode late-life depression. After 8 weeks of treatment with escitalopram or sertraline, serum BDNF levels increased significantly (p=0.026). Binary logistic regression identified male sex (OR=10.094, p=0.007) and the Val/Val genotype (OR=6.559, p=0.003) as independent predictors of treatment efficacy. The study found that male patients carrying the Val/Val genotype responded better to conventional antidepressants, though no significant correlation was found between BDNF level changes and treatment response.

This literature review examines the BDNF Val66Met polymorphism (rs6265) and its association with body weight fluctuations in psychiatric patients. The authors review evidence linking the Val66Met variant to weight changes across multiple psychiatric conditions including schizophrenia, eating disorders, bipolar disorder, major depressive disorder, OCD, and PTSD. The paper proposes the BDNF Val66Met polymorphism as a potential biomarker for monitoring body weight changes in psychiatric patients, noting that Met/Met genotype carriers show greater BMI increases particularly in schizophrenia and bipolar disorder.

This association study examined the BDNF Val66Met polymorphism (rs6265) in 158 subjects (66 schizophrenic, 45 bipolar, 47 healthy controls) using MRI and MR spectroscopy. Met/met homozygotes showed significantly lower NAA/Cre (−21.1%, F(1,52)=4.80, p=0.033) and Glu+Gln/Cre ratios (−46.0%, F(1,52)=6.20, p=0.016) in the left hippocampus compared to val/val homozygotes, providing in vivo evidence for BDNF effects on glutamate system function.

BDNF Val66Met (rs6265) genotype interacts with sex to influence bimanual motor control in healthy humans. Seventy-six participants performed a bimanual motor control task (Preilowski's task) involving line drawing at various angles. The study found a significant genotype-by-sex-by-angle interaction (F(1,65)=4.01, P=0.028), with Val-homozygous females performing significantly worse on difficult angles compared to Met-carrier females (P=0.044), an effect absent in males.

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 cross-generational transmission of anxiety disorders, identifying multiple interconnected pathways including behavioral systems (vicarious learning, parenting style) and biological mechanisms such as prenatal maternal stress and the oxytocinergic system. The oxytocin system (OXTR, rs2254298) emerges as a key biological mechanism linking parent and child anxiety through effects on maternal caregiving sensitivity and anxiety regulation. Gene-by-environment interactions involving genes like OXTR, SLC6A4 (5-HTTLPR), and BDNF interact with early environmental stressors and parenting quality to predict anxiety vulnerability. Epigenetic alterations in OXTR, MAOA, and GAD1 provide evidence for environmental programming of anxiety risk that can persist across generations.

This multicenter cross-sectional study examined 98 multiple sclerosis patients to assess the role of the BDNF Val66Met polymorphism (rs6265) on cognitive and motor disability. The Met allele was found to be protective against cognitive impairment, with Met carriers showing fewer failed neuropsychological tests (β = -1.1, p = 0.027) and better performance on spatial recall tests. Higher EDSS disability scores were associated with progressive disease course but showed only marginal association with the BDNF polymorphism.

Malaguti et al. (2011) examined the role of COMT, 5-HT1A, and SERT genetic polymorphisms in predicting antidepressant response to repetitive transcranial magnetic stimulation (rTMS) in depression patients. The study investigated whether polymorphisms in genes encoding key serotonergic system proteins could predict treatment response to this non-pharmacological antidepressant intervention.

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.

Meta-analysis of 21 case-control studies (7,219 bipolar disorder patients vs 9,832 controls) examining the BDNF Val66Met polymorphism (rs6265, G196A) and bipolar disorder susceptibility. Overall, no significant association was found (pooled OR=1.03, 95% CI 0.98-1.08), though a trend emerged in Caucasians (OR=1.08, P=0.05) and the Val allele showed a protective effect for bipolar II disorder (OR=0.88, P=0.03).

A comprehensive review of genetic modifiers and subtypes in schizophrenia, examining how genetic variation influences clinical heterogeneity across symptoms, age at onset, severity, sex, cognition, and family history. Evidence is reviewed from candidate gene studies and GWAS investigations, including genes like COMT, BDNF, NRG1, ZNF804A, MIR-137, and CSMD1 (rs10503253).

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 association study examined the BDNF Val66Met polymorphism (rs6265) in 301 bipolar disorder patients and 484 healthy controls from India. The Val(G) allele was significantly more frequent in BD patients (OR=1.47, 95% CI=1.11-1.96, χ²=7.08, p=0.008), consistent with European populations. However, no significant association was found between the Val66Met polymorphism and lithium treatment response (N=190 BD subjects).

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).

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 review of post-mortem brain tissue studies examining the neurobiology of suicidal behavior. The paper synthesizes findings on genetic studies, proteomics, neurotransmitter systems (serotonergic, noradrenergic, dopaminergic, glutamatergic), cell signaling, neural plasticity, and neuroendocrinology associated with suicide. Key genetic variants discussed include COMT val158met, TPH2 rs1386494, ADRA2B rs1018351, SLC6A3 rs403636, SAT1 rs6526342, HTR2C Cys23Ser, BDNF Val66Met, and 5-HTTLPR polymorphism.

This study investigated how the BDNF Val66Met polymorphism (rs6265) modulates reward circuitry responses to emotional facial expressions in 29 healthy adults. BDNF V66M genotype explained approximately 30% of the variance in fMRI activation in the orbitofrontal cortex, amygdala, and hippocampus. Val/Val individuals preferentially sought exposure to happy faces and showed stronger activation to aversive stimuli (angry, fearful, sad), while Val/Met carriers showed more balanced responses across emotional expressions.

This paper presents parallel Independent Component Analysis (ICA), a novel multivariate method for jointly analyzing functional MRI and SNP data to identify connections between brain function and genetic variation. Applied to 63 participants (20 schizophrenia patients, 43 controls), the method extracted linked components from 367 SNPs and fMRI data, identifying a genetic component containing SNPs in genes such as DISC1 (rs821616), ADRA2A (rs2429511), and CHRNA7 (rs3087454) that correlated with fMRI-derived brain networks involved in the auditory oddball task.

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 extended genetic linkage analysis to 3D diffusion tensor images (DTI) in 258 twins and siblings to map single gene effects on brain fiber architecture. The BDNF Val66Met polymorphism (rs6265) significantly influenced fractional anisotropy (FA) in the posterior cingulate gyrus, accounting for 90-95% of local FA variance. Raw FA images without smoothing provided greatest sensitivity for detecting gene effects when corrected for multiple comparisons using false discovery rate procedures.

This case-control study of 42 African-American subjects with DSM-III-R schizophrenia examines the BDNF Val66Met variant (rs6265) and its association with age of onset. The study found a significant relationship between BDNF Val66Met genotype and both age of first psychiatric hospitalization (P=0.023) and first schizophrenia symptoms (P=0.006), with Val/Val homozygotes showing later onset than Val/Met heterozygotes.

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.

This review examines genetic and epigenetic factors contributing to anxiety disorder susceptibility, discussing candidate genes including SLC6A4 (serotonin transporter), COMT (catechol-O-methyltransferase), BDNF (brain-derived neurotrophic factor), RGS2 (regulator of G-protein signaling 2), and CRHR1 (corticotropin-releasing hormone receptor 1), and explaining how variants in these genes regulate neurotransmitter systems implicated in anxiety through neurophysiological mechanisms involving the amygdala, prefrontal cortex, and hypothalamic-pituitary-adrenal axis.

Association study of BDNF and LIN-7 genes with adult ADHD using 80 family trios and 121 case-control pairs (201 total probands). Five BDNF SNPs and two LIN-7 SNPs were tested; the functional Val66Met polymorphism (rs6265) and BDNF_2 (rs11030104) showed significant associations after multiple testing correction with odds ratios of 1.65 (p=0.0096) and 1.66 (p=0.0085) respectively. LIN-7_1 (rs10835188) was also significantly associated with adult ADHD.

A comprehensive review of the genetic basis of aggressive behavior, covering candidate genes in neurotransmitter systems (TPH1, TPH2, SLC6A4, DRD4, COMT, MAOA), hypothalamic-pituitary genes (OXT, OXTR, AVPR1A, AVPR1B), and GWAS findings (LRRTM4 rs11126630 p=5.30×10⁻⁸, CDH13 rs11649622 p=4.19×10⁻⁶, FYN rs2148710 p=2.9×10⁻⁸, DYRK1A). The review concludes that genetic predisposition to aggressive behavior involves multiple genes with small individual effects (1-2% each).

Genetic association study of BDNF variants and depression combining two cohort studies (BWHHS, n=3,548; ALSPAC, n=6,838) with meta-analysis of nine publications. The Val66Met variant (rs6265) showed no strong evidence of association with depression (meta-analysis OR=1.06, 95% CI: 0.89-1.26 for MM vs VV genotypes; OR=0.97, 95% CI: 0.89-1.05 for MV vs VV). The C270T polymorphism also showed no evidence of association. Findings suggest BDNF genotype does not exert major influence on development of depression.

This study examined interactive effects of COMT (rs4680, Val158Met) and BDNF (rs6265, Val66Met) polymorphisms on working memory performance and resting-state brain activity in 417 healthy Chinese adults (298 with fMRI data). Significant gene-gene interactions were found for working memory performance and regional homogeneity across multiple frontal brain regions, with COMT-VV/BDNF-VV genotypes showing higher working memory performance and lower frontal ReHo.

This study examined whether the BDNF Val66Met polymorphism (rs6265) influences reading ability and neural activation in 81 children (ages 6-10). Val/Val homozygotes outperformed Met allele carriers on passage comprehension (p=0.042) and phonological memory (p=0.020), and showed lower activation in reading-related brain regions including the fusiform gyrus, left inferior frontal gyrus, left superior temporal gyrus, and hippocampus during reading tasks, suggesting Met carriers require greater neural effort for reading.

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 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 review examines molecular genetic studies of attention-deficit hyperactivity disorder (ADHD) in Han Chinese samples, including candidate gene studies, endophenotype research, genome-wide association studies, and pharmacogenomic investigations. Eight GWAS conducted for ADHD have been inconclusive with no genome-wide significant associations identified, though candidate gene studies have identified associations with dopaminergic (DAT1, DRD4, DRD2, DRD3), noradrenergic (NET1, ADRA2A, ADRA2C), serotonergic (SLC6A4, HTR genes), and metabolic pathway genes (COMT, MAOA, MAOB, DBH, TPH). A meta-analysis of DRD4 longer repeats showed OR=1.70-1.74 in males with ADHD-C subtype.

This family-based association study examined transmission of BDNF variants to 224 bipolar type I patients from a South American population isolate in Colombia. The study found significant excess transmission of the rs6265 G allele (Val66Met) to bipolar cases (χ² = 10.77, P = 0.001), with two-locus haplotype analysis showing significant global transmission distortion (χ² = 16.059, P = 0.025) for a haplotype comprising the rs6265 G allele and a nearby microsatellite allele.

This study analyzed genotype-expression interactions for BDNF across five human brain regions using GTEx data from 300 subjects (985 tissue samples). At FDR < 0.1, 61 SNPs in cerebellum, 55 in cortex, 48 in nucleus accumbens, 47 in caudate, and 58 in cerebellar hemisphere were associated with BDNF expression. Thirty SNPs in two haplotype blocks were shared across all five regions, including rs6265 (Val66Met), rs16917204, rs11030104, and rs6484320, which have been previously associated with psychiatric disorders including depression, bipolar disorder, schizophrenia, OCD, epilepsy, and addiction.