Identification of a Bipolar Disorder Vulnerable Gene CHDH at 3p21.1
文献类型：期刊论文
| 作者 | Rietschel M3; xiaoxiao.whu05@gmail.com; limingkiz@mail.kiz.ac.cn; Chang H1; Li LY1; Xiao X*1; Li M*1; Peng T1; Grigoroiu-Serbanescu M4 |
| 刊名 | Mol Neurobiol
 |
| 出版日期 | 2017 |
| 卷号 | 54期号:X页码:5166–5176 |
| 关键词 | Bipolardisorder Geneexpression Chdh Geneticevidence Expressionquantitativetraitloci(Eqtl) Cognitiveability |
| 英文摘要 | Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome-wide significant levels in studying complex disorders; however, when sample size is limited, the true effects may fail to achieve genome-wide significance. In such case, there may be authentic results among the pools of nominal candidates, and an alternative approach is to consider nominal candidates but are replicable across different samples. Here, we found that mRNA expression of the choline dehydrogenase gene (CHDH) was uniformly upregulated in the brains of bipolar disorder (BPD) patients compared with healthy controls across different studies. Follow-up genetic analyses of CHDH variants in multiple independent clinical datasets (including 11,564 cases and 17,686 controls) identified a risk SNP rs9836592 showing consistent associations with BPD (P meta = 5.72 × 10-4), and the risk allele indicated an increased CHDH expression in multiple neuronal tissues (lowest P = 6.70 × 10-16). These converging results may identify a nominal but true BPD susceptibility gene CHDH. Further exploratory analysis revealed suggestive associations of rs9836592 with childhood intelligence (P = 0.044) and educational attainment (P = 0.0039), a "proxy phenotype" of general cognitive abilities. Intriguingly, the CHDH gene is located at chromosome 3p21.1, a risk region implicated in previous BPD genome-wide association studies (GWAS), but CHDH is lying outside of the core GWAS linkage disequilibrium (LD) region, and our studied SNP rs9836592 is ∼1.2 Mb 3' downstream of the previous GWAS loci (e.g., rs2251219) with no LD between them; thus, the association observed here is unlikely a reflection of previous GWAS signals. In summary, our results imply that CHDH may play a previously unknown role in the etiology of BPD and also highlight the informative value of integrating gene expression and genetic code in advancing our understanding of its biological basis. |
| 语种 | 英语 |
| 资助机构 | This work was supported by CAS Pioneer Hundred Talents Program (to M.L.). This work was also supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Genome Research Network (IG) MooDS (Systematic Investigation of the Molecular Causes of Major Mood Disorders and Schizophrenia; grant 01GS08144 to SC and MMN and grant 01GS08147 to MR), under the auspices of the National Genome Research Network plus (NGFNplus), and through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314A to SC and MMN and grant 01ZX1314G to MR). MMN is a member of the DFG- funded Excellence-Cluster ImmunoSensation. The Romanian sample recruitment and genotyping was funded by UEFISCDI, Bucharest, Romania, grant no. 89/2012 to M.G.S., and by the German Federal Ministry of Education and Research (BMBF), MooDS Project, grant no. 01GS08144 to S.C. and M.M.N. Funding for the Swedish collection was provided by the Stanley Center for Psychiatric Research, Broad Institute, from a grant from Stanley Medical Research Institute. We also wish to thank the BBMRI.se and KI Biobank at Karolinska Institutet for the professional biobank service. ; This work was supported by CAS Pioneer Hundred Talents Program (to M.L.). This work was also supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Genome Research Network (IG) MooDS (Systematic Investigation of the Molecular Causes of Major Mood Disorders and Schizophrenia; grant 01GS08144 to SC and MMN and grant 01GS08147 to MR), under the auspices of the National Genome Research Network plus (NGFNplus), and through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314A to SC and MMN and grant 01ZX1314G to MR). MMN is a member of the DFG- funded Excellence-Cluster ImmunoSensation. The Romanian sample recruitment and genotyping was funded by UEFISCDI, Bucharest, Romania, grant no. 89/2012 to M.G.S., and by the German Federal Ministry of Education and Research (BMBF), MooDS Project, grant no. 01GS08144 to S.C. and M.M.N. Funding for the Swedish collection was provided by the Stanley Center for Psychiatric Research, Broad Institute, from a grant from Stanley Medical Research Institute. We also wish to thank the BBMRI.se and KI Biobank at Karolinska Institutet for the professional biobank service. ; This work was supported by CAS Pioneer Hundred Talents Program (to M.L.). This work was also supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Genome Research Network (IG) MooDS (Systematic Investigation of the Molecular Causes of Major Mood Disorders and Schizophrenia; grant 01GS08144 to SC and MMN and grant 01GS08147 to MR), under the auspices of the National Genome Research Network plus (NGFNplus), and through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314A to SC and MMN and grant 01ZX1314G to MR). MMN is a member of the DFG- funded Excellence-Cluster ImmunoSensation. The Romanian sample recruitment and genotyping was funded by UEFISCDI, Bucharest, Romania, grant no. 89/2012 to M.G.S., and by the German Federal Ministry of Education and Research (BMBF), MooDS Project, grant no. 01GS08144 to S.C. and M.M.N. Funding for the Swedish collection was provided by the Stanley Center for Psychiatric Research, Broad Institute, from a grant from Stanley Medical Research Institute. We also wish to thank the BBMRI.se and KI Biobank at Karolinska Institutet for the professional biobank service. ; This work was supported by CAS Pioneer Hundred Talents Program (to M.L.). This work was also supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Genome Research Network (IG) MooDS (Systematic Investigation of the Molecular Causes of Major Mood Disorders and Schizophrenia; grant 01GS08144 to SC and MMN and grant 01GS08147 to MR), under the auspices of the National Genome Research Network plus (NGFNplus), and through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314A to SC and MMN and grant 01ZX1314G to MR). MMN is a member of the DFG- funded Excellence-Cluster ImmunoSensation. The Romanian sample recruitment and genotyping was funded by UEFISCDI, Bucharest, Romania, grant no. 89/2012 to M.G.S., and by the German Federal Ministry of Education and Research (BMBF), MooDS Project, grant no. 01GS08144 to S.C. and M.M.N. Funding for the Swedish collection was provided by the Stanley Center for Psychiatric Research, Broad Institute, from a grant from Stanley Medical Research Institute. We also wish to thank the BBMRI.se and KI Biobank at Karolinska Institutet for the professional biobank service. |
| 源URL | [http://159.226.149.26:8080/handle/152453/12075]  |
| 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_转化基因组 |
| 通讯作者 | xiaoxiao.whu05@gmail.com; limingkiz@mail.kiz.ac.cn |
| 作者单位 | 1.Key Laboratory ofAnimal Models and Human Disease Mechanisms oftheChineseAcademyofSciencesandYunnanProvince,Kunming Institute of Zoology, Kunming, Yunnan, People’s Republic of China 2.DepartmentofGenomics,LifeandBrainCenter,UniversityofBonn, Bonn, Germany 3.Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany 4.Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania 5.Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden 6.Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA 7.Section of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden 8.Institute of Human Genetics, University of Bonn, Bonn, Germany |
| 推荐引用方式 GB/T 7714 | Rietschel M,xiaoxiao.whu05@gmail.com,limingkiz@mail.kiz.ac.cn,et al. Identification of a Bipolar Disorder Vulnerable Gene CHDH at 3p21.1[J]. Mol Neurobiol,2017,54(X):5166–5176. |
| APA | Rietschel M.,xiaoxiao.whu05@gmail.com.,limingkiz@mail.kiz.ac.cn.,Chang H.,Li LY.,...&Grigoroiu-Serbanescu M.(2017).Identification of a Bipolar Disorder Vulnerable Gene CHDH at 3p21.1.Mol Neurobiol,54(X),5166–5176. |
| MLA | Rietschel M,et al."Identification of a Bipolar Disorder Vulnerable Gene CHDH at 3p21.1".Mol Neurobiol 54.X(2017):5166–5176. |
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来源：昆明动物研究所
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