The gene encoding protocadherin 9 (PCDH9), a novel risk factor for major depressive disorder
文献类型：期刊论文
| 作者 | Luo JX4; Li M*4; Xiao X4; Yao YG2,4; Ma YN1; Chang H4; limingkiz@mail.kiz.ac.cn; Zheng FF3 |
| 刊名 | Neuropsychopharmacology
 |
| 出版日期 | 2017 |
| 卷号 | **期号:**页码:Epub ahead of print |
| 关键词 | Major Depressive Disorder Genome-wide Association Study Meta-analysis Pcdh9 Expression |
| 英文摘要 | ; Genomic analyses have identified only a handful of robust risk loci for major depressive disorder (MDD). In addition to the published genome-wide significant genes, it is believed that there are undiscovered 'treasures' underlying the current MDD genome-wide association studies (GWAS) and gene expression datasets, and digging into these data will allow better understanding of the illness and development of new therapeutic approaches. For this purpose, we performed a meta-analytic study combining three MDD GWAS datasets (23andMe, CONVERGE and PGC), then conducted independent replications of significant loci in two additional samples. The genome-wide significant variants then underwent explorative analyses on MDD related phenotypes, cognitive function alterations and gene expression in brains. In the discovery meta-analysis, a previously unidentified single nucleotide polymorphism (SNP) rs9540720 in the PCDH9 gene was genome-wide significantly associated with MDD (p=1.69 × 10-8 in a total of 89 610 cases and 246 603 controls), and the association was further strengthened when additional replication samples were included (p=1.20 × 10-8 in a total of 136 115 cases and 355 275 controls). The risk SNP was also associated with multiple MDD related phenotypes and cognitive function impairment in diverse samples. Intriguingly, the risk allele of rs9540720 predicted lower PCDH9 expression, which was consistent with the diagnostic analysis results that PCDH9 mRNA expression levels in the brain and peripheral blood tissues were reduced in MDD patients compared with healthy controls. These convergent lines of evidence suggest that PCDH9 is likely a novel risk gene for MDD. Our study highlights the necessity and importance of excavating the public datasets to explore risk genes for MDD, and this approach is also applicable to other complex diseases.Neuropsychopharmacology accepted article preview online, 09 October 2017. |
| 语种 | 英语 |
| 资助机构 | This work was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant NO., XDB13000000), CAS Pioneer Hundred Talents Program (to M.L.), the National Natural Science Foundation of China (81601176 to FZ), the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003 to Y-GY), and the Bureau of Frontier Sciences and Education, Chinese Academy of Sciences (QYZDJ-SSW-SMC005 to Y-GY) ; This work was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant NO., XDB13000000), CAS Pioneer Hundred Talents Program (to M.L.), the National Natural Science Foundation of China (81601176 to FZ), the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003 to Y-GY), and the Bureau of Frontier Sciences and Education, Chinese Academy of Sciences (QYZDJ-SSW-SMC005 to Y-GY) ; This work was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant NO., XDB13000000), CAS Pioneer Hundred Talents Program (to M.L.), the National Natural Science Foundation of China (81601176 to FZ), the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003 to Y-GY), and the Bureau of Frontier Sciences and Education, Chinese Academy of Sciences (QYZDJ-SSW-SMC005 to Y-GY) ; This work was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant NO., XDB13000000), CAS Pioneer Hundred Talents Program (to M.L.), the National Natural Science Foundation of China (81601176 to FZ), the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003 to Y-GY), and the Bureau of Frontier Sciences and Education, Chinese Academy of Sciences (QYZDJ-SSW-SMC005 to Y-GY) |
| 源URL | [http://159.226.149.26:8080/handle/152453/12052]  |
| 专题 | 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 昆明动物研究所_重大疾病机理的遗传学 昆明动物研究所_神经系统疾病 昆明动物研究所_转化基因组 |
| 通讯作者 | limingkiz@mail.kiz.ac.cn |
| 作者单位 | 1.State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China 2.Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences,Shanghai, China 3.Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China 4.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China |
| 推荐引用方式 GB/T 7714 | Luo JX,Li M*,Xiao X,et al. The gene encoding protocadherin 9 (PCDH9), a novel risk factor for major depressive disorder[J]. Neuropsychopharmacology,2017,**(**):Epub ahead of print. |
| APA | Luo JX.,Li M*.,Xiao X.,Yao YG.,Ma YN.,...&Zheng FF.(2017).The gene encoding protocadherin 9 (PCDH9), a novel risk factor for major depressive disorder.Neuropsychopharmacology,**(**),Epub ahead of print. |
| MLA | Luo JX,et al."The gene encoding protocadherin 9 (PCDH9), a novel risk factor for major depressive disorder".Neuropsychopharmacology **.**(2017):Epub ahead of print. |
入库方式： OAI收割
来源：昆明动物研究所
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