Genetic variation withinGRIN2Bin adolescents with alcohol use disorder may be associated with larger left posterior cingulate cortex volume

Abstract

Objective Brain structure differences and adolescent alcohol dependence both show substantial heritability. However, exactly which genes are responsible for brain volume variation in adolescents with substance abuse disorders are currently unknown. The aim of this investigation was to determine whether genetic variants previously implicated in psychiatric disorders are associated with variation in brain volume in adolescents with alcohol use disorder (AUD). Methods The cohort consisted of 58 adolescents with DSM-IV AUD and 58 age and gender- matched controls of mixed ancestry ethnicity. An Illumina Infinium iSelect custom 6000 bead chip was used to genotype 5348 SNPs in 378 candidate genes. Magnetic resonance images were acquired and volumes of global and regional structures were estimated using voxel-based morphometry (VBM). To determine whether any of the genetic variants were associated with brain volume, association analysis was conducted using linear regression in Plink. Results From the exploratory analysis, the GRIN2B SNP rs219927 was associated with brain volume in the left posterior cingulate cortex (p-value< 0.05), whereby having a G-allele was associated with a bigger volume. Conclusion The GRIN2B gene is involved in glutamatergic signalling and may be associated with developmental differences in AUD in brain regions such as the posterior cingulate cortex. Such differences may play a role in risk for AUD, and deserve more detailed investigation.

Brain Anatomical Mediators of GRIN2B Gene Association with Attention/Hyperactivity Problems: An Integrated Genetic-Neuroimaging Study

“…In another pediatric OCD study, a significant association between left orbitofrontal and right anterior cingulate volumes and GRIN2B SNPs emerged [23]. Of note, GRIN2B was linked to left posterior cingulate volume in adolescents with alcohol dependence, one of the disorders most closely related to impulsivity [24]. Since these findings emerged from clinical samples that share only some features with attention deficit syndromes, further investigations are needed to confirm our findings and interpret them in a wider dimensional perspective.…”

“…In Imaging genetics literature, there is evidence of an association between variants in glutamate system genes, including GRIN2B polymorphisms, and neuroimaging phenotypes in healthy and clinical populations [21,22]. Recent magnetic resonance studies have suggested a link between GRIN2B variants and abnormal glutamatergic neurotransmission and brain volume in children and adolescents with obsessive compulsive [23] and alcohol use [24] disorders. Although ADHD has been shown to share symptoms and risk factors with these disorders [25,26], the complex relationships between the GRIN2B gene, brain, and inattention/hyperactivity traits remain largely unknown.…”

A structural MRI study of differential neuromorphometric characteristics of binge and heavy drinking

“…Studies that focused on samples that are akin to more severe HDs, reported morphometric alterations within the precuneus (chronic AUD: ( Durazzo et al, 2014 )) and the posterior cingulate cortex (PCC) (abstinent alcohol dependent patients: ( Rando et al, 2011 )). Interestingly, larger PCC volume was associated with a genetic variant (within GRIN2B) in an adolescent AUD population, suggesting a potential genetic risk component of its neuromorphometric properties ( Dalvie et al, 2017 ).…”

Neurogenomics – towards a more rigorous science

“…Candidate gene association studies with imaging phenotypes continue to be carried out with all of the methodological problems referred to above. Clearly they are still being positively reviewed, both for funding applications and for publication, as they continue to appear in the literature on a regular basis, including these examples just from the last several months: (Bruce et al ., ; Dalvie et al ., ; Gonzalez et al ., ; Jasinska et al ., ; Lubeiro et al ., ; Mallas et al ., ; Swartz et al ., ). This is despite the very solid empirical finding that most, perhaps all, such reported results will not generalise beyond the sample studied.…”