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    Apoptotic engulfment pathway and schizophrenia.

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    Authors
    Chen, Xiangning
    Sun, Cuie
    Chen, Qi
    O'Neill, F Anthony
    Walsh, Dermot
    Fanous, Ayman H
    Chowdari, Kodavali V
    Nimgaonkar, Vishwajit L
    Scott, Adrian
    Schwab, Sibylle G
    Wildenauer, Dieter B
    Che, Ronglin
    Tang, Wei
    Shi, Yongyong
    He, Lin
    Luo, Xiong-Jian
    Su, Bing
    Edwards, Todd L
    Zhao, Zhongming
    Kendler, Kenneth S
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    Affiliation
    Department of Psychiatry and Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, Virginia, USA. xchen@vcu.edu
    Issue Date
    2009
    MeSH
    ATP-Binding Cassette Transporters
    Adaptor Proteins, Signal Transducing
    Apoptosis
    Asian Continental Ancestry Group
    China
    Ethnic Groups
    European Continental Ancestry Group
    Gene Expression Profiling
    Gene Expression Regulation
    Genetic Markers
    Genotype
    Germany
    Humans
    Ireland
    Membrane Proteins
    Schizophrenia
    United States
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    Citation
    Apoptotic engulfment pathway and schizophrenia. 2009, 4 (9):e6875 PLoS ONE
    Journal
    PloS one
    URI
    http://hdl.handle.net/10147/94038
    DOI
    10.1371/journal.pone.0006875
    PubMed ID
    19721717
    Abstract
    BACKGROUND: Apoptosis has been speculated to be involved in schizophrenia. In a previously study, we reported the association of the MEGF10 gene with the disease. In this study, we followed the apoptotic engulfment pathway involving the MEGF10, GULP1, ABCA1 and ABCA7 genes and tested their association with the disease. METHODOLOGY/PRINCIPAL FINDINGS: Ten, eleven and five SNPs were genotyped in the GULP1, ABCA1 and ABCA7 genes respectively for the ISHDSF and ICCSS samples. In all 3 genes, we observed nominally significant associations. Rs2004888 at GULP1 was significant in both ISHDSF and ICCSS samples (p = 0.0083 and 0.0437 respectively). We sought replication in independent samples for this marker and found highly significant association (p = 0.0003) in 3 Caucasian replication samples. But it was not significant in the 2 Chinese replication samples. In addition, we found a significant 2-marker (rs2242436 * rs3858075) interaction between the ABCA1 and ABCA7 genes in the ISHDSF sample (p = 0.0022) and a 3-marker interaction (rs246896 * rs4522565 * rs3858075) amongst the MEGF10, GULP1 and ABCA1 genes in the ICCSS sample (p = 0.0120). Rs3858075 in the ABCA1 gene was involved in both 2- and 3-marker interactions in the two samples. CONCLUSIONS/SIGNIFICANCE: From these data, we concluded that the GULP1 gene and the apoptotic engulfment pathway are involved in schizophrenia in subjects of European ancestry and multiple genes in the pathway may interactively increase the risks to the disease.
    Language
    en
    ISSN
    1932-6203
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pone.0006875
    Scopus Count
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