Background
Neuregulin 1 (NRG1) is one of the leading candidate genes in schizophrenia. Rodents with NRG1 knock-out showed significantly impaired prepulse inhibition (PPI) in the original
report linking NRG1 to schizophrenia. A widely used surrogate measure of psychosis in animal models,
PPI is considered a schizophrenia endophenotype. We hypothesized that if NRG1 influences PPI in rodents, then it should have a similar effect on PPI in humans.
Methods
We examined the potential neurophysiological effects of two nonsynonymous single nucleotide
polymorphisms located on NRG1 (rs3924999 and rs10503929) on PPI. Genotyping was completed in 430 unrelated individuals,
including 244 schizophrenia cases and 186 controls. PPI was available in a subgroup
of 113 cases and 63 controls.
Results
Rs3924999 genotype was significantly associated with PPI (p = .003): PPI was lowest in the subjects who were homozygous for the minor allele
A/A carriers, intermediate in A/G carriers, and highest in homozygous major alleles
G/G carriers. The associations persisted within cases (p = .02) and controls (p = .02) analyzed separately. An additive model suggested that rs3924999 alone contributes
to 7.9% of the PPI variance. In contrast, rs10503929 genotype was not associated with
PPI (p = .85). Schizophrenia patients had reduced PPI compared to control subjects (p = .04). Neither single nucleotide polymorphism was associated with schizophrenia
(all p > .37). However, schizophrenia patients with abnormal PPI may be associated with
rs3924999 (p = .05).
Conclusions
A missense mutation on rs3924999 of the neuregulin 1 gene may have a functional effect
on prepulse inhibition in both schizophrenia and healthy control populations.
Key Words
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Article info
Publication history
Published online: July 15, 2007
Accepted:
May 11,
2007
Received in revised form:
May 10,
2007
Received:
February 27,
2007
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
