GRIN2B mediates susceptibility to affective problems in children and adolescents

Abstract

Objectives

Association studies have implicated the N-methyl-D-aspartate receptor 2B subunit gene (GRIN2B) as candidate for different brain illnesses, also including both internalizing and externalizing disorders. Here, we explored the association between selected SNPs of GRIN2B (rs5796555-/A; rs1012586C/G; rs2268119A/T; rs2216128A/G; rs11609779C/T; rs2192973G/A) and attention problems in children an adolescents as assessed by CBCL 6/18 (Achenbach and Rescorla, 2001).

Methods

In a large cohort of 320 Italian nuclear families selected from an ongoing comprehensive project on child and adolescent psychopathology performed at two sites of our Institutes (BP and UD), we performed a family-based association study to determine whether the GRIN2B gene influence and/or mediates susceptibility to attention problems through time. Genetic association was investigated by the quantitative transmission disequilibrium test (QTDT, version 2.5.1; Abecasis et al., 2000). Quantitative traits were analyzed using the ‘-wega’ and the ‘-ao’ options. Empirical P-values were computed from 10,000 Monte-Carlo permutations, and the significance levels were adjusted by the false discovery rate method (Storey, 2002) applied to the tests performed for each marker (i.e., 8 phenotypes) at two different point times. Latent profile analysis was performed to assess the effect of gene on different trajectories over time. The effect of environmental determinants was also evaluated.

Results

Evidence for significant association of GRIN2B-rs5796555-/A was found with attention problems both at first and second evaluation. Latent profile analysis suggested significant association with specific trajectories and specific environmental factors.

Conclusions

These results provide preliminary evidence of an association between the GRIN2B polymorphism and continuity of attention problems throughout adolescence within an Italian population of referred children and adolescents, suggesting that the GRIN2B genes could play a role in susceptibility to attention problems during developmental age.

Disclosure of interest

The author has not supplied his declaration of competing interest.