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dc.contributor.authorChen, Xiangning
dc.contributor.authorSun, Cuie
dc.contributor.authorChen, Qi
dc.contributor.authorO'Neill, F Anthony
dc.contributor.authorWalsh, Dermot
dc.contributor.authorFanous, Ayman H
dc.contributor.authorChowdari, Kodavali V
dc.contributor.authorNimgaonkar, Vishwajit L
dc.contributor.authorScott, Adrian
dc.contributor.authorSchwab, Sibylle G
dc.contributor.authorWildenauer, Dieter B
dc.contributor.authorChe, Ronglin
dc.contributor.authorTang, Wei
dc.contributor.authorShi, Yongyong
dc.contributor.authorHe, Lin
dc.contributor.authorLuo, Xiong-Jian
dc.contributor.authorSu, Bing
dc.contributor.authorEdwards, Todd L
dc.contributor.authorZhao, Zhongming
dc.contributor.authorKendler, Kenneth S
dc.date.accessioned2010-03-10T10:09:42Z
dc.date.available2010-03-10T10:09:42Z
dc.date.issued2009
dc.identifier.citationApoptotic engulfment pathway and schizophrenia. 2009, 4 (9):e6875 PLoS ONEen
dc.identifier.issn1932-6203
dc.identifier.pmid19721717
dc.identifier.doi10.1371/journal.pone.0006875
dc.identifier.urihttp://hdl.handle.net/10147/94038
dc.description.abstractBACKGROUND: 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.
dc.language.isoenen
dc.subject.meshATP-Binding Cassette Transporters
dc.subject.meshAdaptor Proteins, Signal Transducing
dc.subject.meshApoptosis
dc.subject.meshAsian Continental Ancestry Group
dc.subject.meshChina
dc.subject.meshEthnic Groups
dc.subject.meshEuropean Continental Ancestry Group
dc.subject.meshGene Expression Profiling
dc.subject.meshGene Expression Regulation
dc.subject.meshGenetic Markers
dc.subject.meshGenotype
dc.subject.meshGermany
dc.subject.meshHumans
dc.subject.meshIreland
dc.subject.meshMembrane Proteins
dc.subject.meshSchizophrenia
dc.subject.meshUnited States
dc.titleApoptotic engulfment pathway and schizophrenia.en
dc.contributor.departmentDepartment of Psychiatry and Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, Virginia, USA. xchen@vcu.eduen
dc.identifier.journalPloS oneen
refterms.dateFOA2018-09-03T10:29:23Z
html.description.abstractBACKGROUND: 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.


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