Stress response genes associated with attention deficit hyperactivity disorder: A case-control study in Chinese children

Abstract

To explore the associations between stress response genes and attention deficit hyperactivity disorder (ADHD) in children, we conducted a case-control study consisting of 406 newly diagnosed ADHD cases and 432 controls in Wuhan, China. We genotyped the candidate genes, nuclear receptor subfamily 3 group C member 1(NR3C1) and solute carrier family 6 member 4(SLC6A4), using the Sequenom MassARRAY technology. After correction by Bonferroni (α' = 0.05/6 = 0.008), the rs6191 SNP was found to be associated with a reduced risk of ADHD in the dominant model (OR = 0.564, 95% CI = 0.389-0.819, P = 0.003) while the rs25531 SNP was associated with an increased risk of ADHD in the multiplicative model (OR = 1.380, 95% CI = 1.111-1.714, P = 0.004). Additionally, both the rs6191 and rs25531 SNPs were significantly associated with the attention deficit factor (P = 0.006, P = 0.003, respectively) but not with the hyperactivity/impulsivity factor in the Swanson, Nolan and Pelham-IV Questionnaire (SNAP-IV) scale. Furthermore, we found that these two SNPs were significantly associated with pure ADHD, and not affected by the comorbidities (P = 0.001, P = 0.007, respectively). Besides, there was an interaction between these two SNPs. This study demonstrated the role of NR3C1 and SLC6A4 polymorphisms in ADHD, yet independent replication of the findings of this study in multi-center and multi-stage studies with large samples is warranted in the future.

Keywords: Association; Attention deficit hyperactivity disorder; Gene-gene interaction; Single nucleotide polymorphism; Stress response gene.