rs1611115

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 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 linkage study examined plasma dopamine beta-hydroxylase (pDBH) activity in 284 individuals from 123 families of schizophrenia patients. Strong linkage was confirmed between DBH gene markers and pDBH activity (maximum multipoint LOD score 6.33), with rs1611115 showing the strongest association (p=1.14×10⁻¹⁸). The three key DBH variants rs1611115, rs1611122, and rs6271 accounted for 40% of genetic variation. A novel linkage signal was identified on chromosome 20p12 (LOD=3.1), while no support was found for previously reported linkage on chromosome 19.

This study investigated 12 genetic polymorphisms in four dopamine-related genes (COMT, MAOA, MAOB, and DBH) in 179 incarcerated male Russian adolescents and 242 matched controls to identify genetic associations with aggressive behavior and conduct disorder. The authors found that while individual genetic variants did not differentiate groups, specific combinations of variants (haplotypes) and interactions between variants within and across genes produced informative classifications for incarceration status (P < 0.0001, Nagelkerke R² = 0.141) and conduct disorder diagnosis (P < 0.0001, Nagelkerke R² = 0.158), with a 4-marker model involving COMT rs737865, COMT rs165599, DBH rs1611115, and DBH rs739398 being most predictive.

Association study of DRD4 Ex3 VNTR polymorphism in 107 Polish individuals with behavioral and substance addictions versus 200 healthy controls. Individuals with addiction showed significantly higher frequency of DRD4 Ex3 s/s genotype (67% vs 50% in controls, p=0.0070) and higher combined s allele frequency (0.81 vs 0.69, p=0.0008). Addiction group exhibited elevated STAI trait anxiety and neuroticism scores correlated with s allele genotype.

Development and validation of a targeted NGS panel for diagnosing familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA2), CADASIL, and migraine with aura. In 149 patients across 4 cohorts (55 FHM, 44 CADASIL, 31 EA2, 19 migraine families), the panel identified novel and known mutations in genes CACNA1A, ATP1A2, SCN1A, and NOTCH3, increasing mutation detection rate from 7.7% to 28.5%. Notably, ATP1A2 and NOTCH3 mutations were identified in typical migraine with aura families for the first time, demonstrating aetiological overlap with FHM.

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 case-control association study of 650 German migraine with aura (MA) patients and 650 controls tested 53 variants across 10 dopaminergic system genes. Three SNPs in the dopamine-beta hydroxylase (DBH), dopamine transporter (SLC6A3), and dopamine D2 receptor (DRD2) genes showed significant associations with MA. After gene-wide correction, rs2097629 in DBH (OR=0.77, p=0.0012) and rs40184 in SLC6A3 (OR=0.81, p=0.0082) remained significant, with supporting evidence from 2,937 British controls. These findings provide genetic evidence for dopaminergic system involvement in MA pathogenesis.

This genome-wide association study examined whether parental expressed emotion moderates genetic effects on ADHD symptoms and conduct disorder in 909 family trios (600,000 SNPs genotyped). No gene-by-environment interactions reached genome-wide significance. Nominal effects were observed with 36 uncorrected interaction P-values <10⁻⁵, implicating both novel genes and candidate genes. SNPs in SLC1A1 and NRG3 emerged as candidate genes for follow-up, though the authors emphasize these findings are preliminary and require replication.

This association study examined 28 SNPs across 14 dopamine pathway candidate genes in 403 families with autism to test the hypothesis that common genetic variation in dopamine metabolism contributes to autism susceptibility. While rs2239535 (YWHAB, chromosome 20) showed the strongest nominally significant association (p=0.008), this did not remain significant after correction for multiple comparisons, and no significant gene-gene interactions were detected using Multifactor Dimensionality Reduction analysis.