Apoptotic engulfment pathway and schizophrenia.
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.


RESULTS
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
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.
Chen
Xiangning
X
Department of Psychiatry and Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, Virginia, USA. xchen@vcu.edu
Sun
Cuie
C
Chen
Qi
Q
O'Neill
F Anthony
FA
Walsh
Dermot
D
Fanous
Ayman H
AH
Chowdari
Kodavali V
KV
Nimgaonkar
Vishwajit L
VL
Scott
Adrian
A
Schwab
Sibylle G
SG
Wildenauer
Dieter B
DB
Che
Ronglin
R
Tang
Wei
W
Shi
Yongyong
Y
He
Lin
L
Luo
Xiong-Jian
XJ
Su
Bing
B
Edwards
Todd L
TL
Zhao
Zhongming
Z
Kendler
Kenneth S
KS
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D017209:Apoptosis; D044466:Asian People; D002681:China; D005006:Ethnicity; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005819:Genetic Markers; D005838:Genotype; D005858:Germany; D006801:Humans; D007494:Ireland; D008565:Membrane Proteins / Q000502:physiology*; D012559:Schizophrenia / Q000208:ethnology / Q000503:physiopathology*; D014481:United States; D044465:White People
C577836:ABCA1 protein, human; C411895:ABCA7 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D048868:Adaptor Proteins, Signal Transducing; C454119:GULP1 protein, human; D005819:Genetic Markers; C522055:MEGF10, human; D008565:Membrane Proteins