rs363039

This study examined SNAP25 genetic variants and their association with cognitive performance through both population genetic analysis and association studies. The authors identified that the region carrying rs363039 shows evidence of balancing selection across human populations. In Italian cohorts (368 children aged 3-11 years and 70 neuromuscular patients), heterozygosity for rs363039 was associated with higher verbal performance in females (p=5.8×10⁻⁵ in combined child cohort), while males showed no significant association.

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.

This review of molecular genetic studies of ADHD in Han Chinese populations summarizes candidate gene studies across dopaminergic, noradrenergic, serotonergic, and enzymatic systems, along with the first GWAS in Chinese ADHD cases (n=1040) and controls (n=963). While no single gene has been definitively identified, significant associations include DRD4 7-repeat allele (OR=1.70, 95% CI 1.20-2.40, p=0.003 in males), DBH rs2519152, and various polymorphisms in COMT, NET1, and serotonin genes, though results remain inconsistent across studies.

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 review examines molecular genetic studies of attention-deficit hyperactivity disorder (ADHD) in Han Chinese samples, including candidate gene studies, endophenotype research, genome-wide association studies, and pharmacogenomic investigations. Eight GWAS conducted for ADHD have been inconclusive with no genome-wide significant associations identified, though candidate gene studies have identified associations with dopaminergic (DAT1, DRD4, DRD2, DRD3), noradrenergic (NET1, ADRA2A, ADRA2C), serotonergic (SLC6A4, HTR genes), and metabolic pathway genes (COMT, MAOA, MAOB, DBH, TPH). A meta-analysis of DRD4 longer repeats showed OR=1.70-1.74 in males with ADHD-C subtype.