rs192303

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.

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.

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.

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.