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Acta Neuropsychiatr. 2017 Aug;29(4):252-258. doi: 10.1017/neu.2016.41. Epub 2016 Aug 8.

Genetic variation within GRIN2B in adolescents with alcohol use disorder may be associated with larger left posterior cingulate cortex volume.

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1MRC/UCT Human Genetics Research Unit,Division of Human Genetics,Institute of Infectious Disease and Molecular Medicine,Faculty of Health Sciences,University of Cape Town,Observatory,Cape Town,South Africa.
2Department of Psychiatry and Mental Health,MRC Unit on Anxiety & Stress Disorders,University of Cape Town,Observatory,Cape Town,South Africa.
3Neurobehavioral Research Inc.,Honolulu,HI,United States of America.



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).


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 single nucleotide polymorphisms (SNPs) in 378 candidate genes. Magnetic resonance images were acquired and volumes of global and regional structures were estimated using voxel-based morphometry. To determine whether any of the genetic variants were associated with brain volume, association analysis was conducted using linear regression in Plink.


From the exploratory analysis, the GRIN2B SNP rs219927 was associated with brain volume in the left posterior cingulate cortex (p<0.05), whereby having a G-allele was associated with a bigger volume.


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.


GRIN2B receptor; adolescent; alcoholism; magnetic resonance imaging

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