Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23568192
TITLE
Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.
ABSTRACT
Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64,888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P=6.32 × 10(-5), odds ratio (OR)=1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P<0.005) and the prefrontal cortex (P<1.0 × 10(-6)). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations.
DATE PUBLISHED
2014 Apr
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/11/14
revised 2013/01/28
accepted 2013/03/06
aheadofprint 2013/04/09
entrez 2013/04/10 06:00
pubmed 2013/04/10 06:00
medline 2014/11/18 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Li M Li M M 1] State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China [2] University of Chinese Academy of Sciences, Beijing, China.
Luo XJ Luo X-J XJ University of Rochester Flaum Eye Institute, University of Rochester, Rochester, NY, USA.
Rietschel M Rietschel M M 1] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany [2] Department of Psychiatry, University of Bonn, Bonn, Germany.
Lewis CM Lewis C M CM MRC SGDP Centre, Institute of Psychiatry, King's College London, London, UK.
Mattheisen M Mattheisen M M Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Müller-Myhsok B Müller-Myhsok B B Max Planck Institute of Psychiatry, Munich, Germany.
Jamain S Jamain S S 1] Inserm U 955, IMRB, Psychiatrie Génétique, Créteil, France [2] Fondation Fondamental, Créteil, France.
Leboyer M Leboyer M M 1] Inserm U 955, IMRB, Psychiatrie Génétique, Créteil, France [2] Fondation Fondamental, Créteil, France [3] Pôle de Psychiatrie, AP-HP, Hôpital H. Mondor-A. Chenevier, Créteil, France [4] Faculté de Médecine, Université Paris Est, Créteil, France.
Landén M Landén M M 1] Section of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden [2] Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Thompson PM Thompson P M PM Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Cichon S Cichon S S 1] Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany [2] Department of Genomics, Life and Brain Center and Institute of Human Genetics, University of Bonn, Bonn, Germany.
Nöthen MM Nöthen M M MM 1] Department of Genomics, Life and Brain Center and Institute of Human Genetics, University of Bonn, Bonn, Germany [2] German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Schulze TG Schulze T G TG 1] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany [2] Section on Psychiatric Genetics, Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University, Göttingen, Germany.
Sullivan PF Sullivan P F PF Departments of Genetics, Psychiatry and Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
Bergen SE Bergen S E SE 1] Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA [2] Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Donohoe G Donohoe G G Neuropsychiatric Genetics Group and Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, St James Hospital, Dublin, Ireland.
Morris DW Morris D W DW Neuropsychiatric Genetics Group and Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, St James Hospital, Dublin, Ireland.
Hargreaves A Hargreaves A A Neuropsychiatric Genetics Group and Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, St James Hospital, Dublin, Ireland.
Gill M Gill M M Neuropsychiatric Genetics Group and Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, St James Hospital, Dublin, Ireland.
Corvin A Corvin A A Neuropsychiatric Genetics Group and Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, St James Hospital, Dublin, Ireland.
Hultman C Hultman C C Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Toga AW Toga A W AW Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Shi L Shi L L State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
Lin Q Lin Q Q State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
Shi H Shi H H State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
Gan L Gan L L University of Chinese Academy of Sciences, Beijing, China.
Meyer-Lindenberg A Meyer-Lindenberg A A Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Czamara D Czamara D D Max Planck Institute of Psychiatry, Munich, Germany.
Henry C Henry C C 1] Inserm U 955, IMRB, Psychiatrie Génétique, Créteil, France [2] Fondation Fondamental, Créteil, France [3] Pôle de Psychiatrie, AP-HP, Hôpital H. Mondor-A. Chenevier, Créteil, France [4] Faculté de Médecine, Université Paris Est, Créteil, France.
Etain B Etain B B 1] Inserm U 955, IMRB, Psychiatrie Génétique, Créteil, France [2] Fondation Fondamental, Créteil, France [3] Pôle de Psychiatrie, AP-HP, Hôpital H. Mondor-A. Chenevier, Créteil, France.
Bis JC Bis J C JC Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Ikram MA Ikram M A MA 1] Department of Radiology and Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] The Netherlands Consortium of Healthy Aging, Leiden, The Netherlands.
Fornage M Fornage M M Brown Foundation Institute of Molecular Medicine and Human Genetics Center School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Debette S Debette S S 1] Department of Neurology, Boston University School of Medicine, Boston, MA, USA [2] Institut National de la Santé et de la Recherche Médicale (INSERM), U708, Neuroepidemiology, Paris, France [3] Department of Epidemiology, University of Versailles Saint-Quentin-en-Yvelines, Paris, France.
Launer LJ Launer L J LJ Laboratory of Neurogenetics, Intramural Research Program, National Institute of Aging, NIH, Bethesda, MD, USA.
Seshadri S Seshadri S S 1] Department of Neurology, Boston University School of Medicine, Boston, MA, USA [2] The National, Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
Erk S Erk S S 1] Department of Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany [2] Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, Berlin, Germany.
Walter H Walter H H 1] Department of Psychiatry, University of Bonn, Bonn, Germany [2] Department of Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany [3] Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, Berlin, Germany.
Heinz A Heinz A A Department of Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany.
Bellivier F Bellivier F F 1] Inserm U 955, IMRB, Psychiatrie Génétique, Créteil, France [2] Fondation Fondamental, Créteil, France [3] AP-HP, Hôpital St-Louis-Lariboisière-F Widal, Service Universitaire de Psychiatrie, Paris, France [4] Faculté de Médecine, Université Denis Diderot, Paris, France.
Stein JL Stein J L JL 1] Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA [2] Neurogenetics Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Medland SE Medland S E SE 1] Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia [2] Quantitative Genetics Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia [3] Broad Institute of Harvard and MIT, Boston, MA, USA.
Arias Vasquez A Arias Vasquez A A 1] Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands [2] Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Hibar DP Hibar D P DP Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Franke B Franke B B 1] Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands [2] Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Martin NG Martin N G NG Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Wright MJ Wright M J MJ Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
MooDS Bipolar Consortium
Swedish Bipolar Study Group
Alzheimer’s Disease Neuroimaging Initiative
ENIGMA Consortium
CHARGE Consortium
Su B Su B B State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
INVESTIGATORS
JOURNAL
VOLUME: 19
ISSUE: 4
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2014
MONTH: Apr
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Neuropsychopharmacology. 2010 Jan;35(2):473-82 19829293
Cites Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5;153B(1):10-6 19517574
Cites Biol Psychiatry. 2010 Jul 1;68(1):41-50 20609836
Cites Arch Gen Psychiatry. 2010 Aug;67(8):803-11 20679588
Cites Am J Psychiatry. 2010 Aug;167(8):949-57 20516156
Cites Mol Psychiatry. 2010 Aug;15(8):810-5 19255578
Cites Mol Psychiatry. 2010 Aug;15(8):779-84 20351726
Cites Mol Psychiatry. 2010 Oct;15(10):1016-22 19621016
Cites Bioinformatics. 2010 Oct 1;26(19):2474-6 20702402
Cites Biol Psychiatry. 2011 Feb 15;69(4):353-9 21185011
Cites Am J Hum Genet. 2011 Mar 11;88(3):372-81 21353194
Cites Mol Psychiatry. 2011 Apr;16(4):462-70 20231838
Cites Mol Psychiatry. 2011 May;16(5):473-5 20733578
Cites Neuron. 2011 Apr 28;70(2):252-65 21521612
Cites Schizophr Res. 2011 Jul;129(2-3):217-9 21295948
Cites Hum Mol Genet. 2011 Oct 15;20(20):4076-81 21791550
Cites Nat Genet. 2011 Oct;43(10):977-83 21926972
Cites Mol Psychiatry. 2011 Nov;16(11):1117-29 20838396
Cites Nature. 2011 Oct 27;478(7370):519-23 22031444
Cites Nat Genet. 2012 May;44(5):552-61 22504417
Cites Nat Genet. 2012 May;44(5):545-51 22504421
Cites Genome Res. 2012 Sep;22(9):1790-7 22955989
Cites Nature. 2012 Sep 6;489(7414):57-74 22955616
Cites Nature. 2012 Sep 6;489(7414):75-82 22955617
Cites Nature. 2012 Sep 6;489(7414):83-90 22955618
Cites Nature. 2012 Sep 6;489(7414):91-100 22955619
Cites Nature. 2012 Sep 6;489(7414):101-8 22955620
Cites Nature. 2012 Sep 6;489(7414):109-13 22955621
Cites Psychiatry Res. 2012 Jun 30;198(1):39-46 22386572
Cites Nature. 2012 Nov 1;491(7422):56-65 23128226
Cites Schizophr Res. 2012 Dec;142(1-3):200-5 23102693
Cites Mol Psychiatry. 2013 Mar;18(3):340-6 22212596
Cites BMC Genomics. 2012;13:661 23173617
Cites Mol Psychiatry. 2013 Apr;18(4):497-511 22472876
Cites Mol Psychiatry. 2013 May;18(5):614-7 22565781
Cites Genome Res. 2009 May;19(5):826-37 19307593
Cites Genetics. 2000 Jul;155(3):1405-13 10880498
Cites Biometrics. 1999 Dec;55(4):997-1004 11315092
Cites Hippocampus. 2001;11(6):754-62 11811670
Cites Neuron. 2002 Aug 15;35(4):625-41 12194864
Cites Am J Med Genet. 2002 Dec 8;114(8):980-7 12457397
Cites Arch Gen Psychiatry. 2003 May;60(5):497-502 12742871
Cites Mol Psychiatry. 2003 Jun;8(6):611-8 12851637
Cites Mol Interv. 2002 Oct;2(6):376-91, 339 14993414
Cites Biol Psychiatry. 2004 Aug 1;56(3):151-60 15271583
Cites Neuropsychologia. 1981;19(6):781-93 7329524
Cites Neuropsychologia. 1989;27(1):71-81 2496329
Cites Genetics. 1989 Nov;123(3):585-95 2513255
Cites Genetics. 1993 Mar;133(3):693-709 8454210
Cites Genetics. 1997 Oct;147(2):915-25 9335623
Cites J Med Genet. 1999 Aug;36(8):585-94 10465107
Cites Bioinformatics. 2005 Jan 15;21(2):263-5 15297300
Cites Neurobiol Aging. 2005 Apr;26(4):491-510 15653178
Cites Trends Neurosci. 2005 Aug;28(8):436-45 15982754
Cites Am J Med Genet B Neuropsychiatr Genet. 2005 Aug 5;137B(1):45-50 15999345
Cites Genome Res. 2005 Nov;15(11):1576-83 16251467
Cites Biol Psychiatry. 2006 Jun 15;59(12):1144-50 16457782
Cites Trends Cogn Sci. 2006 Oct;10(10):455-63 16935547
Cites Hum Brain Mapp. 2007 Jun;28(6):464-73 17415783
Cites Am J Hum Genet. 2007 Sep;81(3):559-75 17701901
Cites Biol Psychiatry. 2007 Sep 1;62(5):536-40 17300755
Cites Behav Pharmacol. 2007 Sep;18(5-6):419-30 17762510
Cites Proc Biol Sci. 2007 Nov 22;274(1627):2801-10 17785269
Cites Mol Psychiatry. 2008 Feb;13(2):197-207 17486107
Cites Int J Epidemiol. 2008 Feb;37(1):120-32 17898028
Cites Am J Med Genet B Neuropsychiatr Genet. 2008 Jun 5;147B(4):500-4 18189280
Cites Mol Psychiatry. 2008 Sep;13(9):829, 833-57 18574483
Cites Mol Psychiatry. 2009 Jan;14(1):30-6 18813210
Cites Nat Genet. 2008 Sep;40(9):1056-8 18711365
Cites Bipolar Disord. 2009 Mar;11(2):209-14 19267704
Cites Mol Psychiatry. 2009 Apr;14(4):359-75 19065144
Cites Science. 2009 May 1;324(5927):605 19407193
Cites Nature. 2009 Aug 6;460(7256):748-52 19571811
Cites Science. 2009 Sep 4;325(5945):1246-50 19644074
ErratumIn Mol Psychiatry. 2014 Apr;19(4):527 19644074
GRANTS
GRANTID AGENCY COUNTRY
R01 HD050735 NICHD NIH HHS United States
U24 AG021886 NIA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Age Factors
Aged
Aged, 80 and over
Asian Continental Ancestry Group genetics
Bipolar Disorder genetics
Case-Control Studies genetics
Computational Biology genetics
Cyclic AMP Response Element-Binding Protein genetics
European Continental Ancestry Group genetics
Female genetics
Gene Expression Regulation genetics
Gene Frequency genetics
Genetic Association Studies genetics
Genetic Predisposition to Disease genetics
Hippocampus pathology
Humans pathology
Male pathology
Middle Aged pathology
Neuroimaging pathology
Neuropsychological Tests pathology
Phenotype pathology
Polymorphism, Single Nucleotide genetics
RNA, Messenger metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 CREB1 protein, human
0 Cyclic AMP Response Element-Binding Protein
0 RNA, Messenger
OTHER ID's
OTHERID SOURCE
NIHMS539572 NLM
PMC3937299 NLM