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Neuregulin-1 genotype is associated with structural differences in the normal human brain.

Anna Barnes¹, Matti Isohanni, Jennifer H Barnett

¹Department of Psychiatry, University of Cambridge, Box 189 Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. ab698@cam.ac.uk

|October 25, 2011

Summary

Genetic variation in the neuregulin-1 (NRG-1) gene, specifically SNP8NRG243177, is linked to reduced frontal grey and white matter volumes. This finding may explain how this gene variant contributes to schizophrenia risk.

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Area of Science:

Neurogenetics
Brain Imaging
Psychiatric Genetics

Background:

The neuregulin-1 (NRG-1) gene is crucial for neuronal development and is a candidate gene for schizophrenia.
Previous studies linked NRG-1 variants to white matter alterations, but effects on grey matter volume were unexplored.

Purpose of the Study:

To investigate the voxelwise association between the schizophrenia risk SNP8NRG243177 and brain structure (grey and white matter volume).

Main Methods:

Genotyping of SNP8NRG243177 in 79 participants from the Northern Finland 1966 Birth Cohort (NFBC 1966).
Voxel-based morphometry analysis to assess brain structure variations associated with the SNP.

Main Results:

SNP8NRG243177 T allele carriers exhibited decreased grey matter volume in frontal gyri and anterior cingulate.
Reduced white matter volume was observed in the corpus callosum, corona radiata, internal and external capsules, and tracts like the anterior thalamic radiation and inferior fronto-occipital fasciculus.

Conclusions:

Genetic variation in SNP8NRG243177 influences frontal grey and white matter volumes.
These structural brain changes may represent a mechanism through which this NRG-1 variant confers schizophrenia risk.