title: 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.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine, School of Medicine, Cardiff University, United Kingdom. smithrl8@cf.ac.uk
authors.forename: Rhodri Ll
authors.initials: RL
authors.lastname: Smith
authors.forename: Deborah
authors.initials: D
authors.lastname: Knight
authors.forename: Hywel
authors.initials: H
authors.lastname: Williams
authors.forename: Sarah
authors.initials: S
authors.lastname: Dwyer
authors.forename: Alex
authors.initials: A
authors.lastname: Richards
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
mesh_terms: D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D051579:Neurogranin / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C496649:NRGN protein, human; D051579:Neurogranin