Significant association of GRM7 and GRM8 genes with schizophrenia and major depressive disorder in the Han Chinese population
Significant association of GRM7 and GRM8 genes with schizophrenia and major depressive disorder in the Han Chinese population
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GRM7和GRM8基因与中国汉族人群的精神分裂症和重度抑郁症显着相关
DOI：
10.1016/j.euroneuro.2015.05.004
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发表时间：
2016-01-01
影响因子：
5.6
通讯作者：
Shi, Yongyong
中科院分区：
文献类型：
--
作者：
Li, Wenjin;Ju, Kang;Shi, Yongyong
代谢型谷氨酸受体7型（GRM 7）和8型（GRM 8）参与谷氨酸的神经传递，在精神分裂症（SCZ）和抑郁症（MDD）的发生发展中起重要作用。我们设计了这项研究，以调查是否在GRM 7和GMR 8基因内的常见DNA变异或其遗传相互作用与这些疾病在中国汉族人群。在1235例SCZ患者、1045例MDD患者和1235例正常对照组中选择GRM 7和GRM 8中的14个SNP。在SCZ病例对照受试者中观察到rs 2229902的显著相关性（置换P等位基因= 0.0005，OR=1.492 [95% CI=1.231-1.807]）和rs 9870680 GRM 7中rs 2237781（置换P等位基因= 0.0027，OR =1.346 [95%CI = 1.149-1.575]）。MDD病例对照组的关联分析显示GRM 7的rs779706（置换P等位基因= 0.0099，OR=1.237 [95%CI =1.093-1.399]）和GRM 8的rs 1361995（置换P等位基因= 0.0017，OR=1.488 [95%CI =1.215-1.823]）结果为阳性。此外，在基因-基因互作分析中，由GRM 7和GRM 8多态性构成的三位点模型与MDD显著相关。Meta分析和单倍型分析进一步证实了我们的显著结果。我们证明了GRM 7和GRM 8与SCZ和MDD在中国汉族人群中的遗传关联。我们还发现了这两个基因与两种精神疾病的易感性交互作用，这可能为他们的病因学提供了新的见解。(C)2015 Elsevier B.V.和ECNP。All rights reserved.
Metabotropic glutamate receptor type 7 (GRM7) and type 8 (GRM8) are involved in the neurotransmission of glutamate which is supposed to play an important role in the development of schizophrenia (SCZ) and major depressive disorders (MDD). We designed this study to investigate whether common DNA variants or their genetic interactions within GRM7 and GMR8 genes were associated with these disorders in the Han Chinese population. Fourteen SNPs in GRM7 and GRM8 were selected within a sample set comprising 1235 SCZ patients, 1045 MDD patients and 1235 normal controls. Significant association in SCZ case-control subjects was observed for rs2229902 (permutated P-allele = 0.0005, OR=1.492 [95% CI=1.231-1.807]) and rs9870680 (permutated P-allele=0.0023, OR=1.262 [95% CI=1.116-1.426]) in GRM7 and rs2237781 (permutated P-allele=0.0027, OR=1.346 [95% CI=1.149-1.575]) in GRM8. Association analysis for MDD case-control subjects revealed positive results in rs779706 (permutated P-allele = 0.0099, OR=1.237 [95% CI=1.093-1.399]) of GRM7 and in rs1361995 (permutated P-allele = 0.0017, OR=1.488 [95% CI=1.215-1.823]) of GRM8. Moreover, a three-locus model, constituted by polymorphisms in GRM7 and GRM8 significantly correlated with MDD in the gene gene interaction analysis. Meta-analysis and haplotype analysis further confirmed our significant results. We demonstrated the genetic association of GRM7 and GRM8 with SCZ and MDD in the Han Chinese population. We also found susceptibility interactive effects of these two genes with both psychiatric disorders, which might provide new insights into the etiology of them. (C) 2015 Elsevier B.V. and ECNP. All rights reserved.