Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia
| Autor: | M Athanasiou, Raju Kucherlapati, Todd Lencz, C R Reed, John M. Kane, B Dain, Anil K. Malhotra, T V Morgan |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Psychosis Candidate gene Genetic Linkage Pseudoautosomal region Interleukin-3 Receptor alpha Subunit Mutation Missense Locus (genetics) Biology Polymorphism Single Nucleotide Genetic determinism Cohort Studies Cellular and Molecular Neuroscience Sex Factors medicine Humans Molecular Biology Genetics Genome Human Haplotype medicine.disease Receptors Interleukin-3 Psychiatry and Mental health Haplotypes Receptors Granulocyte-Macrophage Colony-Stimulating Factor Case-Control Studies Schizophrenia Female Interleukin-3 receptor Cytokine receptor |
| Zdroj: | Molecular psychiatry. 12(6) |
| ISSN: | 1359-4184 |
| Popis: | Schizophrenia is a strongly heritable disorder, and identification of potential candidate genes has accelerated in recent years. Genomewide scans have identified multiple large linkage regions across the genome, with fine-mapping studies and other investigations of biologically plausible targets demonstrating several promising candidate genes of modest effect. The recent introduction of technological platforms for whole-genome association (WGA) studies can provide an opportunity to rapidly identify novel targets, although no WGA studies have been reported in the psychiatric literature to date. We report results of a case–control WGA study in schizophrenia, examining B500 000 markers, which revealed a strong effect (P = 3.7 � 10 � 7 ) of a novel locus (rs4129148) near the CSF2RA (colony stimulating factor, receptor 2 alpha) gene in the pseudoautosomal region. Sequencing of CSF2RA and its neighbor, IL3RA (interleukin 3 receptor alpha) in an independent case–control cohort revealed both common intronic haplotypes and several novel, rare missense variants associated with schizophrenia. The presence of cytokine receptor abnormalities in schizophrenia may help explain prior epidemiologic data relating the risk for this illness to altered rates of autoimmune disorders, prenatal infection and familial leukemia. Molecular Psychiatry (2007) 12, 572–580; doi:10.1038/sj.mp.4001983; published online 20 March 2007 |
| Databáze: | OpenAIRE |
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