Supportive evidence for neuregulin 1 as a susceptibility gene for schizophrenia in a Japanese population.
Schizophrenia is a complex genetic disorder and affects approximately 1% of the population worldwide. Recently, Stefansson et al. identified neuregulin 1 (NRG1) on 8p12 as a susceptibility gene for schizophrenia in the Icelandic population. It was reported that the at-risk haplotype ("Hapice") constructed from five SNPs and two microsatellite markers was found to be over-represented in patients with schizophrenia compared to controls. Since then several independent studies have supported the association of NRG1 with schizophrenia. We performed a case-control association study using the four SNPs in a Japanese sample. We genotyped three SNPs (SNP8NRG221533, SNP8NRG241930, and SNP8NRG243177) from Stefansson et al. and one SNP (rs1081062) located in intron 1 of NRG1. There were no significant differences in allele frequencies for each SNP between cases and controls, however, homozygotes of minor alleles in SNP8NRG241930, SNP8NRG243177, and rs1081062 were associated with an increased risk of schizophrenia (P=0.025, OR=4.14; P=0.041, OR=1.43; and P=0.0023, OR=3.06, respectively). Furthermore, the haplotype constructed from four SNPs shows a significant association with schizophrenia (permutation P=0.026). Our data support the hypothesis that NRG1 gene is a susceptibility gene for schizophrenia.
Fukui
Naoki
N
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 757 Asahimachi-ichibancho, Niigata 951-8510, Japan.
Muratake
Tatsuyuki
T
Kaneko
Naoshi
N
Amagane
Hideki
H
Someya
Toshiyuki
T
D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D019317:Evidence-Based Medicine; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020890:Neuregulin-1; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012559:Schizophrenia / Q000208:ethnology* / Q000235:genetics*; D044465:White People / Q000235:genetics
C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1