rs5569

This paper develops and compares two microarray-based genotyping methods (ASO and ASA) for three ADHD-related SNPs: rs1800544 (ADRA2A), rs5569 (SL6CA2), and rs1799971 (OPRM1). The ASA approach demonstrated superior performance with 100% accuracy, shorter analysis time (3 hours), and lower DNA requirement (4 ng) compared to ASO. Both methods enable rapid, cost-effective pharmacogenetic testing suitable for decentralized clinical laboratories.

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 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.

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 examined 11 SLC6A2 gene SNPs in 159 healthy Caucasian volunteers using a double-blind crossover design with placebo and D-amphetamine (10 and 20 mg). SNPs rs36017 and rs1861647 were significantly associated with higher ratings of elation and vigor after 20 mg D-amphetamine, with p-values of 0.033 and 0.002 respectively. Haplotype blocks also showed significant associations with vigor responses.

Haplotype-tagging SNP analysis in 364 individuals from 152 ADHD families identified significant associations between commission errors and SNPs in the DRD2 gene (rs2075654, rs1079596) and between reaction time variability and a SNP in the NET gene (rs3785155). These findings suggest that commission errors and reaction time variability are valid ADHD endophenotypes linked to dopaminergic and noradrenergic pathways.

This family-based association study investigated four ADHD candidate genes (COMT, SLC6A2, MAOA, SLC6A4) for sexually dimorphic genetic effects in 474 ADHD-affected offspring. The Met allele of COMT Val158Met showed stronger association in males (OR=1.42, p=0.003) but not females (p=0.936), and when combined with prior data showed significant gender effects (p=0.007). SLC6A2 and MAOA also showed sex-stratified associations, supporting the hypothesis that ADHD risk genes have sexually dimorphic effects.

This genome-wide association study examined methylphenidate response in 187 children with ADHD using 319,722 SNPs. The most significant association was at P=3×10⁻⁶ (rs9627183 and rs11134178), falling short of genome-wide significance. Two SNPs in the norepinephrine transporter gene (NET/SLC6A2) showed suggestive evidence (rs17841329 and rs192303, P<0.01), while the metabotropic glutamate receptor 7 gene (GRM7, rs3792452) showed the most intriguing association (P=2.6×10⁻⁵), implicating noradrenergic and glutaminergic pathways in methylphenidate response.