rs1843809

A twin study of 1,312 children investigating genetic mediation of endophenotypes in ADHD. Using candidate gene SNPs from dopaminergic, noradrenergic, and serotonergic pathways, the study found the strongest association between rs7984966 in HTR2A and reaction time variability (P=0.007), and rs3785157 in SLC6A2 with commission errors. Mediation analyses revealed that commission errors mediated 38% of the SLC6A2-inattention association, and reaction time variability mediated 44% of the HTR2A-inattention association, suggesting these cognitive measures are intermediate phenotypes on the genetic pathway to ADHD.

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).

Analysis of 554 SNPs across 47 candidate genes in 590 families from the IMAGE ADHD genetics study found no overall parent-of-origin effect (χ² = 1.82, P = 0.117) for ADHD transmission. Five SNP markers in DDC, TPH2, and SLC6A2 showed nominal associations (P < 0.01) with ADHD combined subtype when restricted to maternal or paternal transmission only, but these findings likely represent false positives given multiple comparisons.