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

  • Shareefa Dalvie (a1), Samantha J. Brooks (a2), Valerie Cardenas (a3), George Fein (a3), Raj Ramesar (a1) and Dan J. Stein (a2)...

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 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.

Results

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.

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.

Copyright

Corresponding author

Shareefa Dalvie, Division of Human Genetics, Faculty of Health Sciences, Anzio Road, Observatory, 7925 Cape Town, South Africa. Tel: +27 21 406 6425; Fax: +27 21 650 2010; E-mail: dlvsha006@myuct.ac.za

References

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Tables S1-S2 and Figure S1

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