Functional genetic variation at the NRGN gene and schizophrenia: Evidence from a gene-based case-control study and gene expression analysis
Functional genetic variation at the NRGN gene and schizophrenia: Evidence from a gene-based case-control study and gene expression analysis
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DOI：
10.1002/ajmg.b.32043
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发表时间：
2012-06-01
影响因子：
2.8
通讯作者：
Takeda, Masatoshi
中科院分区：
文献类型：
--
作者：
Ohi, Kazutaka;Hashimoto, Ryota;Takeda, Masatoshi
全基因组关联和随访研究报告了精神分裂症与染色体11q24.2上NRGN基因的rs 12807809之间的关联。我们调查了日本2,019名精神分裂症患者和2,574名对照者中5个连锁不平衡标记的SNP和单倍型与精神分裂症的关联，以确定rs 12807809是否是NRGN基因附近精神分裂症最强相关的变异。我们发现NRGN基因的rs 12807809 rs 12278912单倍型与精神分裂症相关（总体P = 0.001）。0.0042）。rs 12807809 rs 12278912单倍型TG和TA在患者中的频率较高（OR =？1.14，P =？0.0019）和更低（OR =？0.85，P = 0.001。0.0053），分别比对照组。我们没有发现精神分裂症与任何SNPs相关的证据;然而，rs 12278912（OR =？1.10，P？=？0.057）和rs 2075713（OR =？1.10，P？=？0.057）。此外，我们检测到rs 12807809 rs 12278912单倍型和NRGN在45例HapMap JPT受试者的永生化淋巴母细胞中的表达之间的关联（z =？2.69，P =？0.007），并证实了42例精神分裂症患者和44名健康对照者的永生化淋巴母细胞中的相关性（z =？3.09，P = 0.001。0.002）。高风险TG单倍型的表达显著低于保护性TA单倍型。精神分裂症患者的表达低于对照组，但差异无统计学意义。这项研究提供了NRGN基因与精神分裂症相关性的进一步证据，我们的结果表明，TG单倍型rs 12807809 rs 12278912，NRGN表达减少和精神分裂症的风险之间存在联系。(C)2012 Wiley Periodicals，Inc.
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 rs12807809rs12278912 haplotype of the NRGN gene was associated with schizophrenia (global P?=?0.0042). The frequencies of the TG and TA haplotypes of rs12807809rs12278912 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 rs12807809rs12278912 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 rs12807809rs12278912, decreased expression of NRGN and risk of developing schizophrenia. (C) 2012 Wiley Periodicals, Inc.