Combined effect of genetic variants in the GluN2B coding gene (GRIN2B) on prefrontal function during working memory performance

Combined effect of genetic variants in the GluN2B coding gene (GRIN2B) on prefrontal function during working memory performance

The GluN2B subunit of N-methyl-d-aspartate receptors is crucially involved in the physiology of the prefrontal cortex during working memory (WM). Consistently, genetic variants in the GluN2B coding gene (GRIN2B) have been associated with cognitive phenotypes. However, it is unclear how GRIN2B geneti...

Full description

Saved in:
Bibliographic Details
Published in:Psychological medicine Vol. 46; no. 6; p. 1135
Main Authors: Pergola, G, Di Carlo, P, Andriola, I, Gelao, B, Torretta, S, Attrotto, M T, Fazio, L, Raio, A, Albergo, D, Masellis, R, Rampino, A, Blasi, G, Bertolino, A
Format: Journal Article
Language:English
Published: England 01-04-2016
Subjects:
Adolescent
Adult
Aged
Brain Mapping
Female
Humans
Magnetic Resonance Imaging
Male
Memory, Short-Term
Middle Aged
Polymorphism, Single Nucleotide
Prefrontal Cortex - physiopathology
Receptors, N-Methyl-D-Aspartate - genetics
Young Adult
N-methyl-d-aspartate
Expression quantitative trait loci
working memory
GRIN2B
prefrontal cortex
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The GluN2B subunit of N-methyl-d-aspartate receptors is crucially involved in the physiology of the prefrontal cortex during working memory (WM). Consistently, genetic variants in the GluN2B coding gene (GRIN2B) have been associated with cognitive phenotypes. However, it is unclear how GRIN2B genetic variation affects gene expression and prefrontal cognitive processing. Using a composite score, we tested the combined effect of GRIN2B variants on prefrontal activity during WM performance in healthy subjects. We computed a composite score to combine the effects of single nucleotide polymorphisms on post-mortem prefrontal GRIN2B mRNA expression. We then computed the composite score in independent samples of healthy participants in a peripheral blood expression study (n = 46), in a WM behavioural study (n = 116) and in a WM functional magnetic resonance imaging study (n = 122). Five polymorphisms were associated with GRIN2B expression: rs2160517, rs219931, rs11055792, rs17833967 and rs12814951 (all corrected p < 0.05). The score computed to account for their combined effect reliably indexed gene expression. GRIN2B composite score correlated negatively with intelligence quotient, WM behavioural efficiency and dorsolateral prefrontal cortex activity. Moreover, there was a non-linear association between GRIN2B genetic score and prefrontal activity, i.e. both high and low putative genetic score levels were associated with high blood oxygen level-dependent signals in the prefrontal cortex. Multiple genetic variants in GRIN2B are jointly associated with gene expression, prefrontal function and behaviour during WM. These results support the role of GRIN2B genetic variants in WM prefrontal activity in human adults.
ISSN:1469-8978
DOI:10.1017/S0033291715002639