it is well established that adversities and GRIN2B genetic variants (encoding NMDAR GluN2B subunit) are independently associated with behavioral and cognitive impairments in childhood. However, a high proportion of children exposed to risk have good, long-term outcomes.

for the first time, we explored how environmental adversities and GRIN2B genetic variants influence children's cognitive abilities and behavioral problems.

we adopted a gene-by-environment interaction (GxE) approach, to identify children with an unfavorable developmental outcome with the potential of better informing the understanding of susceptibility to developmental disorders.

6 SNPs of GRIN2B were genotyped in 625 children aged 6-11 years from an Italian community-based sample. The interactive effect of GRIN2B variants with 4 measures of adversities (low socioeconomic status - SES, preterm delivery, maternal smoking, absence of breastfeeding) was investigated upon cognitive abilities (vocabulary, block design, forward/backward digit spans of Wechsler's Intelligence Scale, and Rey Figure test) and parents-rated behavioral problems (Child Behavior Checklist/6-18).

rs5796555 x gestational age interaction (p= .00145) influenced cognition, with lower IQ memory among children in the ‘A/A genotype and ≤ 36 gestational age’ group, compared to all other groups. Rs2268119 x SES interaction (p= .00008) influenced behavior, with more attention problems among children in the ‘either A/T or T/T genotype and low SES’ group, compared to all other groups.

GRIN2B targets children with the worst outcome in memory and attention functioning among children exposed to environmental adversities. Identification of children with the highest risk may prompt cost-effective preventive/treatment strategies.