rs11568324

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 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 replication study tested association of two SNPs in the noradrenaline transporter gene (SLC6A2) with ADHD across four independent datasets (IMAGE ST2, Dublin, and MGH samples). rs11568324 showed consistent evidence for a rare protective T allele (OR=0.33-0.34 across datasets, combined P=8×10⁻⁵), while rs3785143 showed weaker and inconsistent association (combined P=0.008, OR=1.3). The rare T allele of rs11568324 (MAF~1%) appears to confer protection against ADHD, though clinical relevance is limited due to its rarity.

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.