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PMID: 19721717 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Apoptotic engulfment pathway and schizophrenia.

PloS one ·Vol. 4 ·No. 9 ·2009-09-01 ·Pages e6875

Chen X, Sun C, Chen Q, O'Neill FA, Walsh D, Fanous AH, Chowdari KV, Nimgaonkar VL, Scott A, Schwab SG, Wildenauer DB, Che R, Tang W, Shi Y, He L, Luo XJ, Su B, Edwards TL, Zhao Z, Kendler KS

Abstract

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. 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. 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.

MeSH Terms
ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters/physiology Adaptor Proteins, Signal Transducing/physiology Apoptosis Asians China Ethnicity Gene Expression Profiling Gene Expression Regulation Genetic Markers Genotype Germany Humans Ireland Membrane Proteins/physiology Schizophrenia/ethnology,physiopathology United States Whites
Chemicals
ABCA1 protein, human ABCA7 protein, human ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters Adaptor Proteins, Signal Transducing GULP1 protein, human Genetic Markers MEGF10, human Membrane Proteins
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Chen Xiangning
Department of Psychiatry and Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, Virginia, USA. [email protected]
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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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0006875
Email
[email protected]
Published
2009-09-01
Epub
2009-00-01
Pages
e6875
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2731162
Subset
IM
Grants
NIMH NIH HHS · R01 MH041953 · United States
NIMH NIH HHS · R01MH41953 · United States
External Links
PubMed source DOI: 10.1371/journal.pone.0006875 PMC Full Text View journal details
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