rs1048101

Case-control study of 216 cervical vertigo patients and 204 controls identifying SNPs in ADRA1A, ADRB1, ADRB2, and NPY genes significantly associated with cervical vertigo risk (ORs 0.62-2.07) and clinical prognosis markers (JOA score and recovery rate). ADRA1A rs3802241 showed OR=2.07 for disease risk and protective effect on prognosis; NPY variants predicted recovery outcomes.

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.

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.

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.

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.

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.

Case-control study examining adrenergic receptor gene polymorphisms in fibromyalgia patients from Mexican and Spanish populations. The beta(2)-AR AC haplotype was a significant risk factor (42.1% in Mexican patients vs 30.5% controls, p=0.04; 50.4% Spanish patients vs 40.0% controls, p=0.05). The rs574584 GG genotype in Mexican patients associated with higher disability scores, morning stiffness, and fatigue.

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.

A family-based association study examined 1005 tag SNPs across 90 genes from five neurotransmission systems (dopaminergic, serotonergic, noradrenergic, GABAergic, and glutamatergic) in 304 bipolar disorder families. Gene-wide significant associations were found for GRIA1 (rs2926835), GRIN2D (rs1799281), and QDPR (rs744731) for allelic associations, and GRIN2C, QDPR, and SLC6A3 for haplotypic associations; however, none survived correction for multiple testing across all systems. The study found no significant SNP associations with comorbid sub-phenotypes or gene-gene interactions, suggesting common variants in these neurotransmission genes do not have major effects on bipolar disorder risk.

This functional study identified nine naturally-occurring human single nucleotide polymorphisms (SNPs) in the α1a-adrenoceptor (ADRA1A) coding region by resequencing 281 individuals from multiple ethnic populations. Seven SNPs resulted in amino acid changes. Using stably transfected rat-1 fibroblasts, the authors demonstrated that four SNPs (R166K, V311I, I200S, and G247R) alter receptor pharmacology and/or biological function: R166K and V311I reduce agonist binding affinity and potency, V311I and I200S alter antagonist binding, and G247R displays increased maximal IP activity with enhanced receptor-G protein coupling (2.1-fold increase in GTPγS binding).

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.