How to Cite this Article: Deng X, Takaki H, Wang L, Kuroki T, Nakahara T, Hashimoto K, Ninomiya H, Arinami T, Inada T, Hiroshi U, Itokawa M, Tochigi M, Watanabe Y, Someya T, Kunugi H, Iwata N, Ozaki N, Shibata H, Fukumaki Y. 2011. Positive Association of Phencyclidine-Responsive Genes, PDE4A and PLAT, With Schizophrenia. Am J Med Genet Part B 156:850–858.
Positive association of Phencyclidine-responsive genes, PDE4A and PLAT, with schizophrenia†
Article first published online: 23 AUG 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 156, Issue 7, pages 850–858, December 2011
How to Cite
Deng, X., Takaki, H., Wang, L., Kuroki, T., Nakahara, T., Hashimoto, K., Ninomiya, H., Arinami, T., Inada, T., Ujike, H., Itokawa, M., Tochigi, M., Watanabe, Y., Someya, T., Kunugi, H., Iwata, N., Ozaki, N., Shibata, H. and Fukumaki, Y. (2011), Positive association of Phencyclidine-responsive genes, PDE4A and PLAT, with schizophrenia. Am. J. Med. Genet., 156: 850–858. doi: 10.1002/ajmg.b.31233
- Issue published online: 6 SEP 2011
- Article first published online: 23 AUG 2011
- Manuscript Accepted: 28 JUL 2011
- Manuscript Received: 19 DEC 2010
- Japan Society for the Promotion of Science (JSPS) for Young Scientists
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Naito Foundation Subsidy for Natural Science Researches
As schizophrenia-like symptoms are produced by administration of phencyclidine (PCP), a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, PCP-responsive genes could be involved in the pathophysiology of schizophrenia. We injected PCP to Wistar rats and isolated five different parts of the brain in 1 and 4 hr after the injection. We analyzed the gene expression induced by the PCP treatment of these tissues using the AGILENT rat cDNA microarray system. We observed changes in expression level in 90 genes and 21 ESTs after the treatment. Out of the 10 genes showing >2-fold expressional change evaluated by qRT-PCR, we selected 7 genes as subjects for the locus-wide association study to identify susceptibility genes for schizophrenia in the Japanese population. In haplotype analysis, significant associations were detected in combinations of two SNPs of BTG2 (P = 1.4 × 10−6), PDE4A (P = 1.4 × 10−6), and PLAT (P = 1 × 10−3), after false discovery rate (FDR) correction. Additionally, we not only successfully replicated the haplotype associations in PDE4A (P = 6.8 × 10−12) and PLAT (P = 0.015), but also detected single-point associations of one SNP in PDE4A (P = 0.0068) and two SNPs in PLAT (P = 0.0260 and 0.0104) in another larger sample set consisting of 2,224 cases and 2,250 controls. These results indicate that PDE4A and PLAT may be susceptibility genes for schizophrenia in the Japanese population. © 2011 Wiley-Liss, Inc.