Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.

Hdl Handle:
http://hdl.handle.net/10147/238822
Title:
Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.
Authors:
O'Dushlaine, C; Kenny, E; Heron, E; Donohoe, G; Gill, M; Morris, D; Corvin, A
Affiliation:
Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
Citation:
Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility. 2011, 16 (3):286-92 Mol. Psychiatry
Journal:
Molecular psychiatry
Issue Date:
Mar-2011
URI:
http://hdl.handle.net/10147/238822
DOI:
10.1038/mp.2010.7
PubMed ID:
20157312
Abstract:
Susceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (P<0.05) to nonsignificant SNPs in a given pathway to identify the 'enrichment' for association signals. We applied this approach to the discovery (the International Schizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03-0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.
Item Type:
Article
Language:
en
MeSH:
Bipolar Disorder; Cell Adhesion Molecules, Neuronal; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Membrane Proteins; Nerve Tissue Proteins; Polymorphism, Single Nucleotide; Schizophrenia; Signal Transduction
ISSN:
1476-5578

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Dushlaine, Cen_GB
dc.contributor.authorKenny, Een_GB
dc.contributor.authorHeron, Een_GB
dc.contributor.authorDonohoe, Gen_GB
dc.contributor.authorGill, Men_GB
dc.contributor.authorMorris, Den_GB
dc.contributor.authorCorvin, Aen_GB
dc.date.accessioned2012-08-15T14:26:34Z-
dc.date.available2012-08-15T14:26:34Z-
dc.date.issued2011-03-
dc.identifier.citationMolecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility. 2011, 16 (3):286-92 Mol. Psychiatryen_GB
dc.identifier.issn1476-5578-
dc.identifier.pmid20157312-
dc.identifier.doi10.1038/mp.2010.7-
dc.identifier.urihttp://hdl.handle.net/10147/238822-
dc.description.abstractSusceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (P<0.05) to nonsignificant SNPs in a given pathway to identify the 'enrichment' for association signals. We applied this approach to the discovery (the International Schizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03-0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Molecular psychiatryen_GB
dc.subject.meshBipolar Disorder-
dc.subject.meshCell Adhesion Molecules, Neuronal-
dc.subject.meshFemale-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMembrane Proteins-
dc.subject.meshNerve Tissue Proteins-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshSchizophrenia-
dc.subject.meshSignal Transduction-
dc.titleMolecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Psychiatry, Trinity College Dublin, Dublin, Ireland.en_GB
dc.identifier.journalMolecular psychiatryen_GB
dc.description.provinceLeinsteren

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