The cAMP responsive element-binding (CREB)-1 gene increases risk of major psychiatric disorders

被引：48
作者：
Xiao, X. [1 ]
Zhang, C. [2 ]
Grigoroiu-Serbanescu, M. [3 ]
Wang, L. [1 ]
Li, L. [1 ]
Zhou, D. [4 ]
Yuan, T-F [5 ]
Wang, C. [6 ,7 ]
Chang, H. [1 ]
Wu, Y. [1 ]
Li, Y. [8 ]
Wu, D-D [9 ]
Yao, Y-G [1 ,10 ]
Li, M. [1 ,10 ]
机构：
[1] Chinese Acad Sci & Yunnan Prov, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, 32 Jiao Chang Donglu, Kunming 650223, Yunnan, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Schizophrenia Program, Shanghai Mental Hlth Ctr, 600 Wan Ping Nan Rd, Shanghai 200030, Peoples R China
[3] Alexandru Obregia Clin Psychiat Hosp, Biometr Psychiat Genet Res Unit, 10 Sos Berceni, Bucharest, Romania
[4] Ningbo Kangning Hosp, Ningbo, Zhejiang, Peoples R China
[5] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, Shanghai, Peoples R China
[6] Ningbo Univ, Sch Med, Dept Pharmacol, Ningbo, Peoples R China
[7] Ningbo Univ, Sch Med, Prov Key Lab Pathophysiol, Ningbo, Zhejiang, Peoples R China
[8] Yunnan Univ, Lab Conservat & Utilizat Bioresource, Kunming, Yunnan, Peoples R China
[9] Chinese Acad Sci, State Key Lab Genet Resources & Evolut, Kunming, Yunnan, Peoples R China
[10] Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai, Peoples R China
来源：
MOLECULAR PSYCHIATRY | 2018年 / 23卷 / 09期
基金：
中国国家自然科学基金;
关键词：
GENOME-WIDE ASSOCIATION; PROTEIN-PROTEIN INTERACTION; SCHIZOPHRENIA GWAS LOCI; BIPOLAR DISORDER; COMMON VARIANTS; EXPRESSION ANALYSIS; MOOD DISORDERS; VRK2; RS2312147; CONFERS RISK; CREB;
D O I：
10.1038/mp.2017.243
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Bipolar disorder (BPD), schizophrenia (SCZ) and unipolar major depressive disorder (MDD) are primary psychiatric disorders sharing substantial genetic risk factors. We previously reported that two single-nucleotide polymorphisms (SNPs) rs2709370 and rs6785 in the cAMP responsive element-binding (CREB)-1 gene (CREB1) were associated with the risk of BPD and abnormal hippocampal function in populations of European ancestry. In the present study, we further expanded our analyses of rs2709370 and rs6785 in multiple BPD, SCZ and MDD data sets, including the published Psychiatric Genomics Consortium (PGC) genome-wide association study, the samples used in our previous CREB1 study, and six additional cohorts (three new BPD samples, two new SCZ samples and one new MDD sample). Although the associations of both CREB1 SNPs with each illness were not replicated in the new cohorts (BPD analysis in 871 cases and 1089 controls (rs2709370, P = 0.0611; rs6785, P = 0.0544); SCZ analysis in 1273 cases and 1072 controls (rs2709370, P = 0.230; rs6785, P = 0.661); and MDD analysis in 129 cases and 100 controls (rs2709370, P = 0.114; rs6785, P = 0.188)), an overall meta-analysis of all included samples suggested that both SNPs were significantly associated with increased risk of BPD (11 105 cases and 51 331 controls; rs2709370, P = 2.33 x 10(-4); rs6785, P = 6.33 x 10(-5)), SCZ (34 913 cases and 44 528 controls; rs2709370, P = 3.96 x 10(-5); rs6785, P = 2.44 x 10(-5)) and MDD (9369 cases and 9619 controls; rs2709370, P = 0.0144; rs6785, P = 0.0314), with the same direction of allelic effects across diagnostic categories. We then examined the impact of diagnostic status on CREB1 mRNA expression using data obtained from independent brain tissue samples, and observed that the mRNA expression of CREB1 was significantly downregulated in psychiatric patients compared with healthy controls. The protein-protein interaction analyses showed that the protein encoded by CREB1 directly interacted with several risk genes of psychiatric disorders identified by GWAS. In conclusion, the current study suggests that CREB1 might be a common risk gene for major psychiatric disorders, and further investigations are necessary.
引用
收藏
页码：1957 / 1967
页数：11
相关论文
共 99 条
  • [51] BDNF Val66Met polymorphism and bipolar disorder in European populations: A risk association in case-control, family-based and GWAS studies[J]. Li, Ming;Chang, Hong;Xiao, Xiao. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 2016
  • [52] Meta-analysis and brain imaging data support the involvement of VRK2 (rs2312147) in schizophrenia susceptibility[J]. Li, Ming;Wang, Yi;Zheng, Xue-bin;Ikeda, Masashi;Iwata, Nakao;Luo, Xiong-jian;Chong, Siow-Ann;Lee, Jimmy;Rietschel, Marcella;Zhang, Fengyu;Mueller-Myhsok, Bertram;Cichon, Sven;Weinberger, Daniel R.;Mattheisen, Manuel;Schulze, Thomas G.;Martin, Nicholas G.;Mitchell, Philip B.;Schofield, Peter R.;Liu, Jian-jun;Su, Bing. SCHIZOPHRENIA RESEARCH, 2012(1-3)
  • [53] A common variant of the cardiomyopathy associated 5 gene (CMYA5) is associated with schizophrenia in Chinese population[J]. Li, Ming;Luo, Xiong-jian;Zhang, Xu;Yang, Zhao-hui;Xiang, Kun;Xiao, Xiao;Su, Bing;Zhao, Ya-li;Xu, Qi;Chen, Xiang-ning;Chen, Jing-chun;Liu, Xing-yan;Yin, Li-de;Ma, Xiao-yuan;Yang, Shun-ying;Yu, Jin;Diao, Hong-bo;Shi, Xiao-dong. SCHIZOPHRENIA RESEARCH, 2011(2-3)
  • [54] Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study[J]. Lichtenstein, Paul;Yip, Benjamin H.;Bjork, Camilla;Pawitan, Yudi;Cannon, Tyrone D.;Sullivan, Patrick F.;Hultman, Christina M. LANCET, 2009(9659)
  • [55] Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder[J]. Liu, Y.;Blackwood, D. H.;Caesar, S.;de Geus, E. J. C.;Farmer, A.;Ferreira, M. A. R.;Ferrier, I. N.;Fraser, C.;Gordon-Smith, K.;Green, E. K.;Grozeva, D.;Gurling, H. M.;Hamshere, M. L.;Heutink, P.;Holmans, P. A.;Hoogendijk, W. J.;Hottenga, J. J.;Jones, L.;Jones, I. R.;Kirov, G.;Lin, D.;McGuffin, P.;Moskvina, V.;Nolen, W. A.;Perlis, R. H.;Posthuma, D.;Scolnick, E. M.;Smit, A. B.;Smit, J. H.;Smoller, J. W.;St Clair, D.;van Dyck, R.;Verhage, M.;Willemsen, G.;Young, A. H.;Zandbelt, T.;Boomsma, D. I.;Craddock, N.;O'Donovan, M. C.;Owen, M. J.;Penninx, B. W. J. H.;Purcell, S.;Sklar, P.;Sullivan, P. F. MOLECULAR PSYCHIATRY, 2011(01)
  • [56] MAOA Variants and Genetic Susceptibility to Major Psychiatric Disorders[J]. Liu, Zichao;Huang, Liang;Luo, Xiong-jian;Wu, Lichuan;Li, Ming. MOLECULAR NEUROBIOLOGY, 2016(07)
  • [57] The Genotype-Tissue Expression (GTEx) project[J]. Lonsdale, John;Thomas, Jeffrey;Salvatore, Mike;Phillips, Rebecca;Lo, Edmund;Shad, Saboor;Hasz, Richard;Walters, Gary;Garcia, Fernando;Young, Nancy;Foster, Barbara;Moser, Mike;Karasik, Ellen;Gillard, Bryan;Ramsey, Kimberley;Sullivan, Susan;Bridge, Jason;Magazine, Harold;Syron, John;Fleming, Johnelle;Siminoff, Laura;Traino, Heather;Mosavel, Maghboeba;Barker, Laura;Jewell, Scott;Rohrer, Dan;Maxim, Dan;Filkins, Dana;Harbach, Philip;Cortadillo, Eddie;Berghuis, Bree;Turner, Lisa;Hudson, Eric;Feenstra, Kristin;Sobin, Leslie;Robb, James;Branton, Phillip;Korzeniewski, Greg;Shive, Charles;Tabor, David;Qi, Liqun;Groch, Kevin;Nampally, Sreenath;Buia, Steve;Zimmerman, Angela;Smith, Anna;Burges, Robin;Robinson, Karna;Valentino, Kim;Bradbury, Deborah. NATURE GENETICS, 2013(06)
  • [58] Function and regulation of CREB family transcription factors in the nervous system[J]. Lonze, BE;Ginty, DD. NEURON, 2002(04)
  • [59] Protein-Protein Interaction and Pathway Analyses of Top Schizophrenia Genes Reveal Schizophrenia Susceptibility Genes Converge on Common Molecular Networks and Enrichment of Nucleosome (Chromatin) Assembly Genes in Schizophrenia Susceptibility Loci[J]. Luo, Xiongjian;Huang, Liang;Jia, Peilin;Li, Ming;Su, Bing;Zhao, Zhongming;Gan, Lin. SCHIZOPHRENIA BULLETIN, 2014(01)
  • [60] Molecular evolution in the CREB1 signal pathway and a rare haplotype in CREB1 with genetic predisposition to schizophrenia[J]. Ma, Liang;Wu, Dong-Dong;Ma, Suk Ling;Tan, Liwen;Chen, Xiaogang;Tang, Nelson L. S.;Yao, Yong-Gang. JOURNAL OF PSYCHIATRIC RESEARCH, 2014
12345678910