Abstract
Genome-wide association and follow-up studies have reported an association between schizophrenia and rs12807809 of the NRGN gene on chromosome 11q24.2. We investigated the association of five linkage disequilibrium-tagging SNPs and haplotypes that cover the NRGN gene with schizophrenia in a Japanese sample of 2,019 schizophrenia patients and 2,574 controls to determine whether rs12807809 is the most strongly associated variant for schizophrenia in the vicinity of the NRGN gene. We found that the rs12807809-rs12278912 haplotype of the NRGN gene was associated with schizophrenia (global P=0.0042). The frequencies of the TG and TA haplotypes of rs12807809-rs12278912 in patients were higher (OR=1.14, P=0.0019) and lower (OR=0.85, P=0.0053), respectively, than in the controls. We did not detect any evidence of association of schizophrenia with any SNPs; however, two nominal associations of rs12278912 (OR=1.10, P=0.057) and rs2075713 (OR=1.10, P=0.057) were observed. Furthermore, we detected an association between the rs12807809-rs12278912 haplotype and NRGN expression in immortalized lymphoblasts derived from 45 HapMap JPT subjects (z=2.69, P=0.007) and confirmed the association in immortalized lymphoblasts derived from 42 patients with schizophrenia and 44 healthy controls (z=3.09, P=0.002). The expression of the high-risk TG haplotype was significantly lower than the protective TA haplotype. The expression was lower in patients with schizophrenia than in controls; however, this difference was not statistically significant. This study provides further evidence of the association of the NRGN gene with schizophrenia, and our results suggest that there is a link between the TG haplotype of rs12807809-rs12278912, decreased expression of NRGN and risk of developing schizophrenia.
| Original language | English |
|---|---|
| Pages (from-to) | 405-413 |
| Number of pages | 9 |
| Journal | American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics |
| Volume | 159 B |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 01-06-2012 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Genetics(clinical)
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
Cite this
}
Functional genetic variation at the NRGN gene and schizophrenia : Evidence from a gene-based case-control study and gene expression analysis. / Ohi, Kazutaka; Hashimoto, Ryota; Yasuda, Yuka; Fukumoto, Motoyuki; Yamamori, Hidenaga; Umeda-Yano, Satomi; Okada, Takeya; Kamino, Kouzin; Morihara, Takashi; Iwase, Masao; Kazui, Hiroaki; Numata, Shusuke; Ikeda, Masashi; Ohnuma, Tohru; Iwata, Nakao; Ueno, Shu ichi; Ozaki, Norio; Ohmori, Tetsuro; Arai, Heii; Takeda, Masatoshi.
In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 159 B, No. 4, 01.06.2012, p. 405-413.Research output: Contribution to journal › Article
TY - JOUR
T1 - Functional genetic variation at the NRGN gene and schizophrenia
T2 - Evidence from a gene-based case-control study and gene expression analysis
AU - Ohi, Kazutaka
AU - Hashimoto, Ryota
AU - Yasuda, Yuka
AU - Fukumoto, Motoyuki
AU - Yamamori, Hidenaga
AU - Umeda-Yano, Satomi
AU - Okada, Takeya
AU - Kamino, Kouzin
AU - Morihara, Takashi
AU - Iwase, Masao
AU - Kazui, Hiroaki
AU - Numata, Shusuke
AU - Ikeda, Masashi
AU - Ohnuma, Tohru
AU - Iwata, Nakao
AU - Ueno, Shu ichi
AU - Ozaki, Norio
AU - Ohmori, Tetsuro
AU - Arai, Heii
AU - Takeda, Masatoshi
PY - 2012/6/1
Y1 - 2012/6/1
N2 - Genome-wide association and follow-up studies have reported an association between schizophrenia and rs12807809 of the NRGN gene on chromosome 11q24.2. We investigated the association of five linkage disequilibrium-tagging SNPs and haplotypes that cover the NRGN gene with schizophrenia in a Japanese sample of 2,019 schizophrenia patients and 2,574 controls to determine whether rs12807809 is the most strongly associated variant for schizophrenia in the vicinity of the NRGN gene. We found that the rs12807809-rs12278912 haplotype of the NRGN gene was associated with schizophrenia (global P=0.0042). The frequencies of the TG and TA haplotypes of rs12807809-rs12278912 in patients were higher (OR=1.14, P=0.0019) and lower (OR=0.85, P=0.0053), respectively, than in the controls. We did not detect any evidence of association of schizophrenia with any SNPs; however, two nominal associations of rs12278912 (OR=1.10, P=0.057) and rs2075713 (OR=1.10, P=0.057) were observed. Furthermore, we detected an association between the rs12807809-rs12278912 haplotype and NRGN expression in immortalized lymphoblasts derived from 45 HapMap JPT subjects (z=2.69, P=0.007) and confirmed the association in immortalized lymphoblasts derived from 42 patients with schizophrenia and 44 healthy controls (z=3.09, P=0.002). The expression of the high-risk TG haplotype was significantly lower than the protective TA haplotype. The expression was lower in patients with schizophrenia than in controls; however, this difference was not statistically significant. This study provides further evidence of the association of the NRGN gene with schizophrenia, and our results suggest that there is a link between the TG haplotype of rs12807809-rs12278912, decreased expression of NRGN and risk of developing schizophrenia.
AB - Genome-wide association and follow-up studies have reported an association between schizophrenia and rs12807809 of the NRGN gene on chromosome 11q24.2. We investigated the association of five linkage disequilibrium-tagging SNPs and haplotypes that cover the NRGN gene with schizophrenia in a Japanese sample of 2,019 schizophrenia patients and 2,574 controls to determine whether rs12807809 is the most strongly associated variant for schizophrenia in the vicinity of the NRGN gene. We found that the rs12807809-rs12278912 haplotype of the NRGN gene was associated with schizophrenia (global P=0.0042). The frequencies of the TG and TA haplotypes of rs12807809-rs12278912 in patients were higher (OR=1.14, P=0.0019) and lower (OR=0.85, P=0.0053), respectively, than in the controls. We did not detect any evidence of association of schizophrenia with any SNPs; however, two nominal associations of rs12278912 (OR=1.10, P=0.057) and rs2075713 (OR=1.10, P=0.057) were observed. Furthermore, we detected an association between the rs12807809-rs12278912 haplotype and NRGN expression in immortalized lymphoblasts derived from 45 HapMap JPT subjects (z=2.69, P=0.007) and confirmed the association in immortalized lymphoblasts derived from 42 patients with schizophrenia and 44 healthy controls (z=3.09, P=0.002). The expression of the high-risk TG haplotype was significantly lower than the protective TA haplotype. The expression was lower in patients with schizophrenia than in controls; however, this difference was not statistically significant. This study provides further evidence of the association of the NRGN gene with schizophrenia, and our results suggest that there is a link between the TG haplotype of rs12807809-rs12278912, decreased expression of NRGN and risk of developing schizophrenia.
UR - http://www.scopus.com/inward/record.url?scp=84860647956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860647956&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.32043
DO - 10.1002/ajmg.b.32043
M3 - Article
C2 - 22461181
AN - SCOPUS:84860647956
VL - 159 B
SP - 405
EP - 413
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
SN - 1552-4841
IS - 4
ER -