Focus 4:350-359, Summer 2006
© 2006 American Psychiatric Association
Neuregulin 1 Transcripts Are Differentially Expressed in Schizophrenia and Regulated by 5' SNPs Associated With the Disease
Amanda J. Law,
Barbara K. Lipska,
Cynthia Shannon Weickert,
Thomas M. Hyde,
Richard E. Straub,
Ryota Hashimoto,
Paul J. Harrison,
Joel E. Kleinman, and
Daniel R. Weinberger
ABSTRACT
Genetic variation in neuregulin 1 (NRG1) is associated with schizophrenia. The disease-associated SNPs are noncoding, and their functional implications remain unknown. We hypothesized that differential expression of the NRG1 gene explains its association to the disease. We examined four of the disease-associated SNPs that make up the original risk haplotype in the 5' upstream region of the gene for their effects on mRNA abundance of NRG1 types I–IV in human postmortem hippocampus. Diagnostic comparisons revealed a 34% increase in type I mRNA in schizophrenia and an interaction of diagnosis and genotype (SNP8NRG221132) on this transcript. Of potentially greater interest, a single SNP within the risk haplotype (SNP8NRG243177) and a 22-kb block of this core haplotype are associated with mRNA expression for the novel type IV isoform in patients and controls. Bioinformatic promoter analyses indicate that both SNPs lead to a gain/loss of putative binding sites for three transcription factors, serum response factor, myelin transcription factor-1, and High Mobility Group Box Protein-1. These data implicate variation in isoform expression as a molecular mechanism for the genetic association of NRG1 with schizophrenia.
(Reprinted with permission from
PNAS April 25, 2006; 103(17):6747–6752[Abstract/Free Full Text]
© 2006 by The National Academy of Sciences of the USA)
Get information about faster international access.
Privacy Policy
Copyright © 2006
American Psychiatric Association.
All rights reserved.
Home
| Search
| Current Issue
| Past Issues
| Subscribe
| All APPI Journals
| Help
| Contact Us
|
