Journal article
Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia
Human molecular genetics, v 17(20), pp 3212-3222
15 Oct 2008
PMID: 18658164
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Abstract
Schizophrenia is a complex mental disorder with a fairly high degree of heritability. Although the causes of schizophrenia remain unclear, it is now widely accepted that it is a neurodevelopmental and neurodegenerative disorder involving disconnectivity and disorder of the synapses. Disrupted-in-schizophrenia 1 (DISC1) is a promising candidate susceptibility gene involved in neurodevelopment, including maturation of the cerebral cortex. To identify other susceptibility genes for schizophrenia, we screened for DISC1-interacting molecules [NudE-like (NUDEL), Lissencephaly-1 (LIS1), 14-3-3epsilon (YWHAE), growth factor receptor bound protein 2 (GRB2) and Kinesin family 5A of Kinesen1 (KIF5A)], assessing a total of 25 tagging single-nucleotide polymorphisms (SNPs) in a Japanese population. We identified a YWHAE SNP (rs28365859) that showed a highly significant difference between case and control samples, with higher minor allele frequencies in controls (P(allele) = 1.01 x 10(-5) and P(genotype) = 4.08 x 10(-5) in 1429 cases and 1728 controls). Both messenger RNA transcription and protein expression of 14-3-3epsilon were also increased in the lymphocytes of healthy control subjects harboring heterozygous and homozygous minor alleles compared with homozygous major allele subjects. To further investigate a potential role for YWHAE in schizophrenia, we studied Ywhae(+/-) mice in which the level of 14-3-3epsilon protein is reduced to 50% of that in wild-type littermates. These mice displayed weak defects in working memory in the eight-arm radial maze and moderately enhanced anxiety-like behavior in the elevated plus-maze. Our results suggest that YWHAE is a possible susceptibility gene that functions protectively in schizophrenia.
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Details
- Title
- Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia
- Creators
- Masashi Ikeda - Fujita Health UniversityTakao Hikita - Nagoya UniversityShinichiro Taya - Nagoya UniversityJunko Uraguchi-Asaki - Nagoya UniversityKazuhito Toyo-oka - University of California San DiegoAnthony Wynshaw-Boris - University of California San DiegoHiroshi Ujike - Okayama UniversityToshiya Inada - Seiwa HospitalKeizo Takao - Fujita Health UniversityTsuyoshi Miyakawa - College Station Medical CenterNorio Ozaki - Nagoya UniversityKozo Kaibuchi - Nagoya UniversityNakao Iwata - Department of Psychiatry
- Publication Details
- Human molecular genetics, v 17(20), pp 3212-3222
- Publisher
- Oxford Univ Press
- Number of pages
- 11
- Grant note
- nstitute for Bioinformatics Research and Development (BIRD) Japan Science and Technology Agency (JST); Japan Science & Technology Agency (JST) Japan Society for the Promotion of Science; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Ministry of Health, Labour and Welfare; Ministry of Health, Labour and Welfare, Japan Japan Health Sciences Foundation (Research on Health Sciences Focusing on Drug Innovation) 17025021 / Ministry of Education, Culture, Sports, Science and Technology of Japan; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) 21st Century Center of Excellence Program; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Neuroinformatics Japan Center (NIJC), RIKEN
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000259766800011
- Scopus ID
- 2-s2.0-53349156385
- Other Identifier
- 991020099717304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Genetics & Heredity