Analysis of neurogranin (NRGN) in schizophrenia.

Abstract

A recent study reported a genome-wide significant association between schizophrenia and rs12807809-a SNP located approximately 3 kbp upstream of the neurogranin gene (NRGN). We sought to determine if (a) NRGN contains common exonic variants or variants affecting expression (eQTLs) that could account for the association with rs12807809 and (b) there exist rare non-synonymous highly penetrant variants that could potentially confer high risk of schizophrenia. We sequenced all four exons of NRGN in a screening set of 14 individuals but found no novel common polymorphisms. We additionally sequenced the coding exons in up to 1,113 individuals (699 cases) but this revealed only a singleton-coding variant in exon 2 (G246T leading to Gly-55 → Val amino acid change) in which prediction of function analysis suggested is likely to be benign. Finally, analysis of a brain expression dataset of at least 130 individuals did not identify any eQTLs that were correlated with associated SNP rs12807809 following correction for multiple testing.

• Authors: Rhodri Ll Smith, Deborah Knight, Hywel Williams, Sarah Dwyer, Alex Richards, George Kirov, Michael C O'Donovan, Michael J Owen
• Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 156B Issue 5 Pg. 532-5 (Jul 2011) ISSN: 1552-485X [Electronic] United States
• PMID: 21538840 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley-Liss, Inc.

Chemical References

• NRGN protein, human
• Neurogranin

Topics

• Alleles
• Base Sequence
• Case-Control Studies
• Gene Expression
• Genetic Predisposition to Disease
• Genotype
• Humans
• Neurogranin (genetics)
• Polymerase Chain Reaction
• Polymorphism, Single Nucleotide
• Schizophrenia (genetics)
• Sequence Analysis, DNA