Apoptotic engulfment pathway and schizophrenia.

Hdl Handle:
http://hdl.handle.net/10147/94038
Title:
Apoptotic engulfment pathway and schizophrenia.
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
Affiliation:
Department of Psychiatry and Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, Virginia, USA. xchen@vcu.edu
Citation:
Apoptotic engulfment pathway and schizophrenia. 2009, 4 (9):e6875 PLoS ONE
Journal:
PloS one
Issue Date:
2009
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
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
ISSN:
1932-6203

Full metadata record

DC FieldValue Language
dc.contributor.authorChen, Xiangningen
dc.contributor.authorSun, Cuieen
dc.contributor.authorChen, Qien
dc.contributor.authorO'Neill, F Anthonyen
dc.contributor.authorWalsh, Dermoten
dc.contributor.authorFanous, Ayman Hen
dc.contributor.authorChowdari, Kodavali Ven
dc.contributor.authorNimgaonkar, Vishwajit Len
dc.contributor.authorScott, Adrianen
dc.contributor.authorSchwab, Sibylle Gen
dc.contributor.authorWildenauer, Dieter Ben
dc.contributor.authorChe, Ronglinen
dc.contributor.authorTang, Weien
dc.contributor.authorShi, Yongyongen
dc.contributor.authorHe, Linen
dc.contributor.authorLuo, Xiong-Jianen
dc.contributor.authorSu, Bingen
dc.contributor.authorEdwards, Todd Len
dc.contributor.authorZhao, Zhongmingen
dc.contributor.authorKendler, Kenneth Sen
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

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