rs362584

Directed mutation screening and tag SNP association analysis of SNAP25 in 662 UK schizophrenic cases and 716 controls identified significant associations at rs3746544 (P=0.004, OR=1.26) and rs8636 (P=0.003, OR=1.27), both of which survive permutation correction. Additional tag SNP analysis revealed rs3787283 (P=0.006, OR=1.25) and several nominally associated SNPs. Notably, the schizophrenia risk alleles are opposite to ADHD protective alleles at the same loci, suggesting differential allelic effects across psychiatric disorders.

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.

Dense mapping study of SNAP-25 gene in 229 ADHD families found nominally significant association with rs3787283 (P=0.002) in strong linkage disequilibrium with previously implicated SNPs rs3746544 and rs1051312 (D'=0.89-0.94). Meta-analysis pooling data from five prior studies showed modest support for rs3746544 (P=0.048) and rs6077690 (P=0.031). Exploratory phenotype analysis revealed the strongest associations in ADHD patients with co-morbid major depressive disorder, where six SNPs and a haplotype block showed significant association (P=0.012-0.045).