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Association analysis of the Cadherin13 gene with schizophrenia in the Japanese population

Authors Otsuka I, Watanabe Y, Hishimoto A, Boku S, Mouri K, Shiroiwa K, Okazaki S, Nunokawa A, Shirakawa O, Someya T, Sora I

Received 16 March 2015

Accepted for publication 13 April 2015

Published 2 June 2015 Volume 2015:11 Pages 1381—1393


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Wai Kwong Tang

Ikuo Otsuka,1 Yuichiro Watanabe,2 Akitoyo Hishimoto,1 Shuken Boku,1 Kentaro Mouri,1 Kyoichi Shiroiwa,1 Satoshi Okazaki,1 Ayako Nunokawa,2 Osamu Shirakawa,3 Toshiyuki Someya,2 Ichiro Sora1

1Department of Psychiatry, Graduate School of Medicine, Kobe University, Kobe, 2Department of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 3Department of Neuropsychiatry, School of Medicine, Kinki University, Osaka, Japan

Background: Cadherin13 (CDH13) is a glycosylphosphatidylinositol-anchored cell adhesion molecule that plays a crucial role in morphogenesis and the maintenance of neuronal circuitry. CDH13 has been implicated in the susceptibility to a variety of psychiatric diseases. A recent genome-wide association study using Danish samples showed, for the first time, the involvement of a single nucleotide polymorphism (SNP) of CDH13 (intronic SNP rs8057927) in schizophrenia. Here, we investigated the association between other SNPs of CDH13 and schizophrenia and tried to replicate the association for the SNP of rs8057927, in the Japanese population.
Methods: Using TaqMan® SNP genotyping assays, five tag SNPs (rs12925602, rs7193788, rs736719, rs6565051, and rs7204454) in the promoter region of CDH13 were examined for their association with schizophrenia in two independent samples. The first sample comprised 665 patients and 760 controls, and the second sample comprised 677 patients and 667 controls. One tag SNP for rs8057927 was also examined for the association with schizophrenia in the first sample set.
Results: A GACAG haplotype of the five SNPs in the promoter region of CDH13 was significantly associated with schizophrenia in the first sample set (P=0.016 and corrected P=0.098). A combined analysis of the GACAG haplotype with the second sample set enhanced the significance (P=0.0026 and corrected P=0.021). We found no association between rs8057927 and schizophrenia in the first sample set.
Conclusion: Our results suggest that CDH13 may contribute to the genetic risk of schizophrenia. Further replication on the association of CDH13 with schizophrenia and functional studies are required to confirm the current findings.

Keywords: CDH13, promoter region, haplotype, SNP

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