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Apoptotic engulfment pathway and schizophrenia

Chen, X and Sun, C and Chen, Q and O'Neill, FA and Walsh, D and Fanous, AH and Chowdari, KV and Nimgaonkar, VL and Scott, A and Schwab, SG and Wildenauer, DB and Che, R and Tang, W and Shi, Y and He, L and Luo, XJ and Su, B and Edwards, TL and Zhao, Z and Kendler, KS (2009) Apoptotic engulfment pathway and schizophrenia. PLoS ONE, 4 (9).

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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. © 2009 Chen et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Chen, X
Sun, C
Chen, Q
O'Neill, FA
Walsh, D
Fanous, AH
Chowdari, KV
Nimgaonkar, VLnimga@pitt.eduNIMGA
Scott, A
Schwab, SG
Wildenauer, DB
Che, R
Tang, W
Shi, Y
He, L
Luo, XJ
Su, B
Edwards, TL
Zhao, Z
Kendler, KS
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 September 2009
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 4
Number: 9
DOI or Unique Handle: 10.1371/journal.pone.0006875
Refereed: Yes
MeSH Headings: ATP-Binding Cassette Transporters--physiology; Adaptor Proteins, Signal Transducing--physiology; 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--physiology; Schizophrenia--ethnology; Schizophrenia--physiopathology; United States
Other ID: NLM PMC2731162
PubMed Central ID: PMC2731162
PubMed ID: 19721717
Date Deposited: 03 Aug 2012 16:17
Last Modified: 05 Feb 2019 16:55


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