Association and interaction analyses of NRG1 and ERBB4 genes with schizophrenia in a Japanese population.
Neuregulin 1 (NRG1) is one of the most promising candidate genes for schizophrenia. A number of replication studies have been conducted, although the results were inconsistent and no susceptible variant has yet been identified. The inconsistency might be attributed to the ethnic difference in allele and haplotype frequencies. However, it is equally possible that one or more genes interacting with NRG1 may also be implicated in schizophrenia and attribute to the inconsistency. To test the hypothesis, we conducted an interaction analysis between NRG1 and one of its receptor's (ERBB4) polymorphisms as well as the association analysis of the two genes associated with schizophrenia in Japanese. We observed no significant difference between patients and controls in allele frequencies or genotypic distributions of the 18 polymorphisms of the genes. The permutation test showed no significant differences in estimated haplotype frequencies between patients and controls, including the haplotype HAP(ICE). In the interaction analysis, significant interaction was observed between rs2919381 in NRG1 and rs7560730 in ERBB4 (P = 0.047, corrected). Thus, our results suggest the possibility that interaction between variants in NRG1 and ERBB4 might contribute to susceptibility for schizophrenia in a Japanese population. Further investigation may be necessary to confirm our results.
Shiota
Sae
S
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.
Tochigi
Mamoru
M
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.
Shimada
Hiroko
H
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.
Ohashi
Jun
J
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.
Kasai
Kiyoto
K
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.
Kato
Nobumasa
N
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.
Tokunaga
Katsushi
K
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.
Sasaki
Tsukasa
T
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan. psytokyo@yahoo.co.jp.|Health Service Center, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan. psytokyo@yahoo.co.jp.
D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020890:Neuregulin-1; D020641:Polymorphism, Single Nucleotide; D066247:Receptor, ErbB-4; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology
C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4