Apoptotic Engulfment Pathway and Schizophrenia

Authors

Xiangning Chen, Virginia Commonwealth UniversityFollow
Cuie Sun, Virginia Commonwealth University
Qi Chen, Virginia Commonwealth University
F. Anthony O'Neill, The Queens University, Belfast
Dermot Walsh, The Health Research Board
Ayman H. Fanous, Washington VA Medical Center
Kodavali V. Chowdari, University of Pittsburgh School of Medicine
Vishwajit L. Nimgaonkar, University of Pittsburgh School of Medicine
Adrian Scott, University of Western Australia
Sibylle G. Schwab, University of Western Australia
Dieter B. Wildenauer, University of Western Australia
Ronglin Che, Shanghai Jiao Tong University
Wei Tang, Shanghai Jiao Tong University
Yongyong Shi, Shanghai Jiao Tong University
Lin He, Shanghai Jiao Tong University
Xiong-jian Luo, Chinese Academy of Sciences
Bing Su, Chinese Academy of Sciences
Todd L. Edwards, University of Miami
Zhongming Zhao, Vanderbilt University School of Medicine
Kenneth S. Kendler, Virginia Commonwealth UniversityFollow

Document Type

Article

Original Publication Date

2009

Journal/Book/Conference Title

PLOS ONE

Volume

4

DOI of Original Publication

10.1371/journal.pone.0006875

Comments

Originally Published at http://dx.doi.org/10.1371/journal.pone.0006875

Date of Submission

November 2014

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 ABCA7genes 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.

Rights

Copyright: © 2009 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Human and Molecular Genetics Publications