S22.01 - A Neuregulin 1 variant associated with altered brain structure and function

Abstract

Introduction:

Neuregulin 1 is a replicated susceptibility gene for schizophrenia with effects on neuronal migration, axon guidance and myelination. A specific variant of NRG1, SNP8NRG243177, has been found to be associated with NRG1 expression although to date no study has established whether this variant is associated with altered brain structure or function in human subjects.

Methods:

Data from 2 studies was used for our analyses. First we examined the effects of SNP8NRG243177 on IQ, Psychotic symptoms and cortical function in the Edinburgh High Risk Study. Secondly, we examined the effects of the same variant on white matter using T1 estimated white matter density and an analysis of fractional anisotropy (FA).

Results:

The SNP8NRG243177 T allele is associated with psychotic symptoms, IQ and altered fronto-temporal function in people at high risk of schizophrenia for familial reasons. Secondly, we found that the same variant is associated with reduced density and integrity of white matter at the top of the internal capsule.

Conclusions:

Our results add to a growing body of animal and human work supporting a mechanistic role for NRG1 in the aetiology of schizophrenia.