Synaptosome-related (SNARE) genes and their interactions contribute to the susceptibility and working memory of attention-deficit/hyperactivity disorder in males

• SNARE complex was critical in fusion and showed association with psychiatric disorders, including ADHD.
• Distribution of genotypes of rs875342 of STX1A was significantly different between ADHD and controls.
• Rs363039 of SNAP25 and rs1150 of VAMP2, showed association with RCFT scores of ADHD while rs875342 of STX1A with digit span.
• Significant joint action was found between SNARE genes.
• SNARE complex genes may act as independent influencing factor or component of gene-gene interaction in susceptibility and working memory of ADHD in males.

BackgroundsN-ethylmaleimide-sensitive attachment protein receptor (SNARE) complex involved in neurotransmission via exocytosis was implicated in attention-deficit/hyperactivity disorder (ADHD). The present study investigated the influence of SNARE related genes and their interaction on ADHD susceptibility and their cognitive functions.MethodsWe genotyped eight single nucleotide polymorphisms (SNP) of Syntaxin 1A (STX1A), vesicle-associated membrane protein 2 (VAMP2) and synaptosomal-associated protein 25 kDa (SNAP25) and conducted case-control studies in 1404 male ADHD and 617 male controls. Quantitative analyses were performed for genotypes and performance on the Rey–Osterrieth complex figure test (RCFT), digit span test and Stroop test in 383 ADHD males. In addition, we explored gene–gene interactions by generalized multifactor dimensionality reduction (GMDR) followed with logistic regression and analyses of covariance for verifying.ResultsGenotypic distribution of rs875342 of STX1A was significantly different between ADHD and controls. The SNPs, rs363039 of SNAP25 and rs1150 of VAMP2, were significantly associated with RCFT scores, while rs875342 of STX1A with digit span. We found genetic interaction models between these three genes and ADHD susceptibility as well as working memory function evaluated by RCFT.ConclusionSNARE complex genes and their interactions may play a significant role in susceptibility and working memory of ADHD.

The identified best model showed a significant association with ADHD presence (P < 0.001) by GMDR. In each cell, the left bar represents a positive score, and the right bar a negative score. High-risk cells are indicated by dark shading, low-risk cells by light shading, and empty cells by no shading. Note that the patterns of high-risk and low-risk cells differ across each of the different multilocus dimensions, presenting evidence of epistasis.Figure optionsDownload as PowerPoint slide