BRIEF REPORTSGenetic association between Notch4 polymorphisms and Japanese schizophrenicsShibata, Nobutoa; Ohnuma, Tohrua; Higashi, Shinjia; Higashi, Maikoa; Usui, Chiea; Ohkubo, Takua; Watanabe, Tomokoa; Kitajima, Akiyoshia; Ueki, Akirab; Nagao, Masatsuguc; Arai, Heiia Author Information aDepartment of Psychiatry, Juntendo University School of Medicine, Bunkyo-ku, Tokyo bDepartment of Neurology, Omiya Medical Center, Jichi Medical School, Saitama-shi, Saitama cDepartment of Psychiatry, Nagao Hospital, kure-shi Hiroshima, Japan Correspondence and requests for reprints to Nobuto Shibata MD, Department of Psychiatry, Juntendo University School of Medicine. 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan Tel: +81 3 5802 1071; fax: +81 3 5802 1071; e-mail: [email protected] Sponsorship: This study was in part funded by a High Technology Research Center Grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology and by a research grant from the Japanese Ministry of Health, Labour and Welfare of Japan. Received 21 September 2005 Accepted 28 December 2005 Psychiatric Genetics: April 2006 - Volume 16 - Issue 2 - p 77-79 doi: 10.1097/01.ypg.0000194442.81813.b9 Buy Metrics Abstract The objective of this study was to investigate whether three single nucleotide polymorphisms of the Notch4 gene are associated with the onset of schizophrenia. To confirm the linkage disequilibrium among these three single nucleotide polymorphisms of the gene, the three single nucleotide polymorphisms were genotyped by a polymerase chain reaction-restriction-fragment length polymorphism method for all samples. The genotypic frequencies of each single nucleotide polymorphism in the schizophrenic were compared with respective controls using a χ2 method. To check linkage disequilibrium, the haplotype frequency program was utilized. No statistical association between the two single nucleotide polymorphisms of the Notch4 gene and schizophrenia was observed in our Japanese samples. Although one nonsynonymous single nucleotide polymorphism did show a weakly significant P-value, its allelic frequencies are not positive. Two of the single nucleotide polymorphisms showed strong linkage disequilibrium in our Japanese samples. The single nucleotide polymorphism between the other two single nucleotide polymorphisms showed a weaker linkage disequilibrium with the others. Our study suggests that the three single nucleotide polymorphisms are not associated with the onset of schizophrenia. The linkage disequilibrium of this locus indicates that there is genetic heterogeneity in the Notch4 gene. Linkage disequilibrium may differ among ethnic groups, and so a larger study should be performed in this region. © 2006 Lippincott Williams & Wilkins, Inc.