Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.
Identifieur interne : 003839 ( PubMed/Corpus ); précédent : 003838; suivant : 003840Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.
Auteurs : M. Li ; X-J Luo ; M. Rietschel ; C M Lewis ; M. Mattheisen ; B. Müller-Myhsok ; S. Jamain ; M. Leboyer ; M. Landén ; P M Thompson ; S. Cichon ; M M Nöthen ; T G Schulze ; P F Sullivan ; S E Bergen ; G. Donohoe ; D W Morris ; A. Hargreaves ; M. Gill ; A. Corvin ; C. Hultman ; A W Toga ; L. Shi ; Q. Lin ; H. Shi ; L. Gan ; A. Meyer-Lindenberg ; D. Czamara ; C. Henry ; B. Etain ; J C Bis ; M A Ikram ; M. Fornage ; S. Debette ; L J Launer ; S. Seshadri ; S. Erk ; H. Walter ; A. Heinz ; F. Bellivier ; J L Stein ; S E Medland ; A. Arias Vasquez ; D P Hibar ; B. Franke ; N G Martin ; M J Wright ; B. SuSource :
- Molecular psychiatry [ 1476-5578 ] ; 2014.
English descriptors
- KwdEn :
- Adult, Age Factors, Aged, Aged, 80 and over, Asian Continental Ancestry Group (genetics), Bipolar Disorder (ethnology), Bipolar Disorder (genetics), Case-Control Studies, Computational Biology, Cyclic AMP Response Element-Binding Protein (genetics), European Continental Ancestry Group (genetics), Female, Gene Expression Regulation (genetics), Gene Frequency (genetics), Genetic Association Studies, Genetic Predisposition to Disease, Hippocampus (pathology), Humans, Male, Middle Aged, Neuroimaging, Neuropsychological Tests, Phenotype, Polymorphism, Single Nucleotide (genetics), RNA, Messenger (metabolism).
- MESH :
- chemical , genetics : Cyclic AMP Response Element-Binding Protein.
- ethnology : Bipolar Disorder.
- genetics : Asian Continental Ancestry Group, Bipolar Disorder, European Continental Ancestry Group, Gene Expression Regulation, Gene Frequency, Polymorphism, Single Nucleotide.
- chemical , metabolism : RNA, Messenger.
- pathology : Hippocampus.
- Adult, Age Factors, Aged, Aged, 80 and over, Case-Control Studies, Computational Biology, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Neuroimaging, Neuropsychological Tests, Phenotype.
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.
DOI: 10.1038/mp.2013.37
PubMed: 23568192
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pubmed:23568192Le document en format XML
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Li</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Luo, X J" sort="Luo, X J" uniqKey="Luo X" first="X-J" last="Luo">X-J Luo</name><affiliation><nlm:affiliation>University of Rochester Flaum Eye Institute, University of Rochester, Rochester, NY, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rietschel, M" sort="Rietschel, M" uniqKey="Rietschel M" first="M" last="Rietschel">M. Rietschel</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Lewis, C M" sort="Lewis, C M" uniqKey="Lewis C" first="C M" last="Lewis">C M Lewis</name><affiliation><nlm:affiliation>MRC SGDP Centre, Institute of Psychiatry, King's College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Mattheisen, M" sort="Mattheisen, M" uniqKey="Mattheisen M" first="M" last="Mattheisen">M. Mattheisen</name><affiliation><nlm:affiliation>Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Muller Myhsok, B" sort="Muller Myhsok, B" uniqKey="Muller Myhsok B" first="B" last="Müller-Myhsok">B. Müller-Myhsok</name><affiliation><nlm:affiliation>Max Planck Institute of Psychiatry, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Jamain, S" sort="Jamain, S" uniqKey="Jamain S" first="S" last="Jamain">S. Jamain</name><affiliation><nlm:affiliation>1] Inserm U 955, IMRB, Psychiatrie Génétique, Créteil, France [2] Fondation Fondamental, Créteil, France.</nlm:affiliation></affiliation></author><author><name sortKey="Leboyer, M" sort="Leboyer, M" uniqKey="Leboyer M" first="M" last="Leboyer">M. Leboyer</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Landen, M" sort="Landen, M" uniqKey="Landen M" first="M" last="Landén">M. Landén</name><affiliation><nlm:affiliation>1] Section of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden [2] Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Thompson, P M" sort="Thompson, P M" uniqKey="Thompson P" first="P M" last="Thompson">P M Thompson</name><affiliation><nlm:affiliation>Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Cichon, S" sort="Cichon, S" uniqKey="Cichon S" first="S" last="Cichon">S. Cichon</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Nothen, M M" sort="Nothen, M M" uniqKey="Nothen M" first="M M" last="Nöthen">M M Nöthen</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Schulze, T G" sort="Schulze, T G" uniqKey="Schulze T" first="T G" last="Schulze">T G Schulze</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Sullivan, P F" sort="Sullivan, P F" uniqKey="Sullivan P" first="P F" last="Sullivan">P F Sullivan</name><affiliation><nlm:affiliation>Departments of Genetics, Psychiatry and Epidemiology, University of North Carolina, Chapel Hill, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bergen, S E" sort="Bergen, S E" uniqKey="Bergen S" first="S E" last="Bergen">S E Bergen</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Donohoe, G" sort="Donohoe, G" uniqKey="Donohoe G" first="G" last="Donohoe">G. Donohoe</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Morris, D W" sort="Morris, D W" uniqKey="Morris D" first="D W" last="Morris">D W Morris</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Hargreaves, A" sort="Hargreaves, A" uniqKey="Hargreaves A" first="A" last="Hargreaves">A. Hargreaves</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Gill, M" sort="Gill, M" uniqKey="Gill M" first="M" last="Gill">M. Gill</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Corvin, A" sort="Corvin, A" uniqKey="Corvin A" first="A" last="Corvin">A. Corvin</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Hultman, C" sort="Hultman, C" uniqKey="Hultman C" first="C" last="Hultman">C. Hultman</name><affiliation><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Toga, A W" sort="Toga, A W" uniqKey="Toga A" first="A W" last="Toga">A W Toga</name><affiliation><nlm:affiliation>Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Shi, L" sort="Shi, L" uniqKey="Shi L" first="L" last="Shi">L. Shi</name><affiliation><nlm:affiliation>State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.</nlm:affiliation></affiliation></author><author><name sortKey="Lin, Q" sort="Lin, Q" uniqKey="Lin Q" first="Q" last="Lin">Q. Lin</name><affiliation><nlm:affiliation>State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.</nlm:affiliation></affiliation></author><author><name sortKey="Shi, H" sort="Shi, H" uniqKey="Shi H" first="H" last="Shi">H. Shi</name><affiliation><nlm:affiliation>State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.</nlm:affiliation></affiliation></author><author><name sortKey="Gan, L" sort="Gan, L" uniqKey="Gan L" first="L" last="Gan">L. Gan</name><affiliation><nlm:affiliation>University of Chinese Academy of Sciences, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Meyer Lindenberg, A" sort="Meyer Lindenberg, A" uniqKey="Meyer Lindenberg A" first="A" last="Meyer-Lindenberg">A. Meyer-Lindenberg</name><affiliation><nlm:affiliation>Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Czamara, D" sort="Czamara, D" uniqKey="Czamara D" first="D" last="Czamara">D. Czamara</name><affiliation><nlm:affiliation>Max Planck Institute of Psychiatry, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Henry, C" sort="Henry, C" uniqKey="Henry C" first="C" last="Henry">C. Henry</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Etain, B" sort="Etain, B" uniqKey="Etain B" first="B" last="Etain">B. Etain</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Bis, J C" sort="Bis, J C" uniqKey="Bis J" first="J C" last="Bis">J C Bis</name><affiliation><nlm:affiliation>Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Ikram, M A" sort="Ikram, M A" uniqKey="Ikram M" first="M A" last="Ikram">M A Ikram</name><affiliation><nlm:affiliation>1] Department of Radiology and Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] The Netherlands Consortium of Healthy Aging, Leiden, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Fornage, M" sort="Fornage, M" uniqKey="Fornage M" first="M" last="Fornage">M. Fornage</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Debette, S" sort="Debette, S" uniqKey="Debette S" first="S" last="Debette">S. Debette</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Launer, L J" sort="Launer, L J" uniqKey="Launer L" first="L J" last="Launer">L J Launer</name><affiliation><nlm:affiliation>Laboratory of Neurogenetics, Intramural Research Program, National Institute of Aging, NIH, Bethesda, MD, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Seshadri, S" sort="Seshadri, S" uniqKey="Seshadri S" first="S" last="Seshadri">S. Seshadri</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Erk, S" sort="Erk, S" uniqKey="Erk S" first="S" last="Erk">S. Erk</name><affiliation><nlm:affiliation>1] Department of Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany [2] Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Walter, H" sort="Walter, H" uniqKey="Walter H" first="H" last="Walter">H. Walter</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Heinz, A" sort="Heinz, A" uniqKey="Heinz A" first="A" last="Heinz">A. Heinz</name><affiliation><nlm:affiliation>Department of Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Bellivier, F" sort="Bellivier, F" uniqKey="Bellivier F" first="F" last="Bellivier">F. Bellivier</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Stein, J L" sort="Stein, J L" uniqKey="Stein J" first="J L" last="Stein">J L Stein</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Medland, S E" sort="Medland, S E" uniqKey="Medland S" first="S E" last="Medland">S E Medland</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Arias Vasquez, A" sort="Arias Vasquez, A" uniqKey="Arias Vasquez A" first="A" last="Arias Vasquez">A. Arias Vasquez</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Hibar, D P" sort="Hibar, D P" uniqKey="Hibar D" first="D P" last="Hibar">D P Hibar</name><affiliation><nlm:affiliation>Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Franke, B" sort="Franke, B" uniqKey="Franke B" first="B" last="Franke">B. Franke</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Martin, N G" sort="Martin, N G" uniqKey="Martin N" first="N G" last="Martin">N G Martin</name><affiliation><nlm:affiliation>Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Wright, M J" sort="Wright, M J" uniqKey="Wright M" first="M J" last="Wright">M J Wright</name><affiliation><nlm:affiliation>Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Su, B" sort="Su, B" uniqKey="Su B" first="B" last="Su">B. Su</name><affiliation><nlm:affiliation>State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:23568192</idno><idno type="pmid">23568192</idno><idno type="doi">10.1038/mp.2013.37</idno><idno type="wicri:Area/PubMed/Corpus">003839</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003839</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.</title><author><name sortKey="Li, M" sort="Li, M" uniqKey="Li M" first="M" last="Li">M. Li</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Luo, X J" sort="Luo, X J" uniqKey="Luo X" first="X-J" last="Luo">X-J Luo</name><affiliation><nlm:affiliation>University of Rochester Flaum Eye Institute, University of Rochester, Rochester, NY, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rietschel, M" sort="Rietschel, M" uniqKey="Rietschel M" first="M" last="Rietschel">M. Rietschel</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Lewis, C M" sort="Lewis, C M" uniqKey="Lewis C" first="C M" last="Lewis">C M Lewis</name><affiliation><nlm:affiliation>MRC SGDP Centre, Institute of Psychiatry, King's College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Mattheisen, M" sort="Mattheisen, M" uniqKey="Mattheisen M" first="M" last="Mattheisen">M. Mattheisen</name><affiliation><nlm:affiliation>Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Muller Myhsok, B" sort="Muller Myhsok, B" uniqKey="Muller Myhsok B" first="B" last="Müller-Myhsok">B. Müller-Myhsok</name><affiliation><nlm:affiliation>Max Planck Institute of Psychiatry, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Jamain, S" sort="Jamain, S" uniqKey="Jamain S" first="S" last="Jamain">S. Jamain</name><affiliation><nlm:affiliation>1] Inserm U 955, IMRB, Psychiatrie Génétique, Créteil, France [2] Fondation Fondamental, Créteil, France.</nlm:affiliation></affiliation></author><author><name sortKey="Leboyer, M" sort="Leboyer, M" uniqKey="Leboyer M" first="M" last="Leboyer">M. Leboyer</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Landen, M" sort="Landen, M" uniqKey="Landen M" first="M" last="Landén">M. Landén</name><affiliation><nlm:affiliation>1] Section of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden [2] Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Thompson, P M" sort="Thompson, P M" uniqKey="Thompson P" first="P M" last="Thompson">P M Thompson</name><affiliation><nlm:affiliation>Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Cichon, S" sort="Cichon, S" uniqKey="Cichon S" first="S" last="Cichon">S. Cichon</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Nothen, M M" sort="Nothen, M M" uniqKey="Nothen M" first="M M" last="Nöthen">M M Nöthen</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Schulze, T G" sort="Schulze, T G" uniqKey="Schulze T" first="T G" last="Schulze">T G Schulze</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Sullivan, P F" sort="Sullivan, P F" uniqKey="Sullivan P" first="P F" last="Sullivan">P F Sullivan</name><affiliation><nlm:affiliation>Departments of Genetics, Psychiatry and Epidemiology, University of North Carolina, Chapel Hill, NC, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bergen, S E" sort="Bergen, S E" uniqKey="Bergen S" first="S E" last="Bergen">S E Bergen</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Donohoe, G" sort="Donohoe, G" uniqKey="Donohoe G" first="G" last="Donohoe">G. Donohoe</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Morris, D W" sort="Morris, D W" uniqKey="Morris D" first="D W" last="Morris">D W Morris</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Hargreaves, A" sort="Hargreaves, A" uniqKey="Hargreaves A" first="A" last="Hargreaves">A. Hargreaves</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Gill, M" sort="Gill, M" uniqKey="Gill M" first="M" last="Gill">M. Gill</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Corvin, A" sort="Corvin, A" uniqKey="Corvin A" first="A" last="Corvin">A. Corvin</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Hultman, C" sort="Hultman, C" uniqKey="Hultman C" first="C" last="Hultman">C. Hultman</name><affiliation><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Toga, A W" sort="Toga, A W" uniqKey="Toga A" first="A W" last="Toga">A W Toga</name><affiliation><nlm:affiliation>Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Shi, L" sort="Shi, L" uniqKey="Shi L" first="L" last="Shi">L. Shi</name><affiliation><nlm:affiliation>State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.</nlm:affiliation></affiliation></author><author><name sortKey="Lin, Q" sort="Lin, Q" uniqKey="Lin Q" first="Q" last="Lin">Q. Lin</name><affiliation><nlm:affiliation>State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.</nlm:affiliation></affiliation></author><author><name sortKey="Shi, H" sort="Shi, H" uniqKey="Shi H" first="H" last="Shi">H. Shi</name><affiliation><nlm:affiliation>State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.</nlm:affiliation></affiliation></author><author><name sortKey="Gan, L" sort="Gan, L" uniqKey="Gan L" first="L" last="Gan">L. Gan</name><affiliation><nlm:affiliation>University of Chinese Academy of Sciences, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Meyer Lindenberg, A" sort="Meyer Lindenberg, A" uniqKey="Meyer Lindenberg A" first="A" last="Meyer-Lindenberg">A. Meyer-Lindenberg</name><affiliation><nlm:affiliation>Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Czamara, D" sort="Czamara, D" uniqKey="Czamara D" first="D" last="Czamara">D. Czamara</name><affiliation><nlm:affiliation>Max Planck Institute of Psychiatry, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Henry, C" sort="Henry, C" uniqKey="Henry C" first="C" last="Henry">C. Henry</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Etain, B" sort="Etain, B" uniqKey="Etain B" first="B" last="Etain">B. Etain</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Bis, J C" sort="Bis, J C" uniqKey="Bis J" first="J C" last="Bis">J C Bis</name><affiliation><nlm:affiliation>Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Ikram, M A" sort="Ikram, M A" uniqKey="Ikram M" first="M A" last="Ikram">M A Ikram</name><affiliation><nlm:affiliation>1] Department of Radiology and Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] The Netherlands Consortium of Healthy Aging, Leiden, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Fornage, M" sort="Fornage, M" uniqKey="Fornage M" first="M" last="Fornage">M. Fornage</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Debette, S" sort="Debette, S" uniqKey="Debette S" first="S" last="Debette">S. Debette</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Launer, L J" sort="Launer, L J" uniqKey="Launer L" first="L J" last="Launer">L J Launer</name><affiliation><nlm:affiliation>Laboratory of Neurogenetics, Intramural Research Program, National Institute of Aging, NIH, Bethesda, MD, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Seshadri, S" sort="Seshadri, S" uniqKey="Seshadri S" first="S" last="Seshadri">S. Seshadri</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Erk, S" sort="Erk, S" uniqKey="Erk S" first="S" last="Erk">S. Erk</name><affiliation><nlm:affiliation>1] Department of Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany [2] Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Walter, H" sort="Walter, H" uniqKey="Walter H" first="H" last="Walter">H. Walter</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Heinz, A" sort="Heinz, A" uniqKey="Heinz A" first="A" last="Heinz">A. Heinz</name><affiliation><nlm:affiliation>Department of Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Bellivier, F" sort="Bellivier, F" uniqKey="Bellivier F" first="F" last="Bellivier">F. Bellivier</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Stein, J L" sort="Stein, J L" uniqKey="Stein J" first="J L" last="Stein">J L Stein</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Medland, S E" sort="Medland, S E" uniqKey="Medland S" first="S E" last="Medland">S E Medland</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Arias Vasquez, A" sort="Arias Vasquez, A" uniqKey="Arias Vasquez A" first="A" last="Arias Vasquez">A. Arias Vasquez</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Hibar, D P" sort="Hibar, D P" uniqKey="Hibar D" first="D P" last="Hibar">D P Hibar</name><affiliation><nlm:affiliation>Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Franke, B" sort="Franke, B" uniqKey="Franke B" first="B" last="Franke">B. Franke</name><affiliation><nlm:affiliation>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.</nlm:affiliation></affiliation></author><author><name sortKey="Martin, N G" sort="Martin, N G" uniqKey="Martin N" first="N G" last="Martin">N G Martin</name><affiliation><nlm:affiliation>Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Wright, M J" sort="Wright, M J" uniqKey="Wright M" first="M J" last="Wright">M J Wright</name><affiliation><nlm:affiliation>Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Su, B" sort="Su, B" uniqKey="Su B" first="B" last="Su">B. Su</name><affiliation><nlm:affiliation>State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Molecular psychiatry</title><idno type="eISSN">1476-5578</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Age Factors</term><term>Aged</term><term>Aged, 80 and over</term><term>Asian Continental Ancestry Group (genetics)</term><term>Bipolar Disorder (ethnology)</term><term>Bipolar Disorder (genetics)</term><term>Case-Control Studies</term><term>Computational Biology</term><term>Cyclic AMP Response Element-Binding Protein (genetics)</term><term>European Continental Ancestry Group (genetics)</term><term>Female</term><term>Gene Expression Regulation (genetics)</term><term>Gene Frequency (genetics)</term><term>Genetic Association Studies</term><term>Genetic Predisposition to Disease</term><term>Hippocampus (pathology)</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Neuroimaging</term><term>Neuropsychological Tests</term><term>Phenotype</term><term>Polymorphism, Single Nucleotide (genetics)</term><term>RNA, Messenger (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cyclic AMP Response Element-Binding Protein</term></keywords><keywords scheme="MESH" qualifier="ethnology" xml:lang="en"><term>Bipolar Disorder</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Asian Continental Ancestry Group</term><term>Bipolar Disorder</term><term>European Continental Ancestry Group</term><term>Gene Expression Regulation</term><term>Gene Frequency</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>RNA, Messenger</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Hippocampus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Age Factors</term><term>Aged</term><term>Aged, 80 and over</term><term>Case-Control Studies</term><term>Computational Biology</term><term>Female</term><term>Genetic Association Studies</term><term>Genetic Predisposition to Disease</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Neuroimaging</term><term>Neuropsychological Tests</term><term>Phenotype</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23568192</PMID><DateCreated><Year>2014</Year><Month>03</Month><Day>24</Day></DateCreated><DateCompleted><Year>2014</Year><Month>11</Month><Day>17</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1476-5578</ISSN><JournalIssue CitedMedium="Internet"><Volume>19</Volume><Issue>4</Issue><PubDate><Year>2014</Year><Month>Apr</Month></PubDate></JournalIssue><Title>Molecular psychiatry</Title><ISOAbbreviation>Mol. Psychiatry</ISOAbbreviation></Journal><ArticleTitle>Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.</ArticleTitle><Pagination><MedlinePgn>452-61</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/mp.2013.37</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Li</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Luo</LastName><ForeName>X-J</ForeName><Initials>XJ</Initials><AffiliationInfo><Affiliation>University of Rochester Flaum Eye Institute, University of Rochester, Rochester, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rietschel</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lewis</LastName><ForeName>C M</ForeName><Initials>CM</Initials><AffiliationInfo><Affiliation>MRC SGDP Centre, Institute of Psychiatry, King's College London, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mattheisen</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Müller-Myhsok</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Max Planck Institute of Psychiatry, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jamain</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>1] Inserm U 955, IMRB, Psychiatrie Génétique, Créteil, France [2] Fondation Fondamental, Créteil, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Leboyer</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Landén</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>1] Section of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden [2] Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thompson</LastName><ForeName>P M</ForeName><Initials>PM</Initials><AffiliationInfo><Affiliation>Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cichon</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nöthen</LastName><ForeName>M M</ForeName><Initials>MM</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schulze</LastName><ForeName>T G</ForeName><Initials>TG</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sullivan</LastName><ForeName>P F</ForeName><Initials>PF</Initials><AffiliationInfo><Affiliation>Departments of Genetics, Psychiatry and Epidemiology, University of North Carolina, Chapel Hill, NC, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bergen</LastName><ForeName>S E</ForeName><Initials>SE</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Donohoe</LastName><ForeName>G</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Morris</LastName><ForeName>D W</ForeName><Initials>DW</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hargreaves</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gill</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Corvin</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hultman</LastName><ForeName>C</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Toga</LastName><ForeName>A W</ForeName><Initials>AW</Initials><AffiliationInfo><Affiliation>Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shi</LastName><ForeName>L</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Q</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shi</LastName><ForeName>H</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gan</LastName><ForeName>L</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>University of Chinese Academy of Sciences, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meyer-Lindenberg</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Czamara</LastName><ForeName>D</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Max Planck Institute of Psychiatry, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Henry</LastName><ForeName>C</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Etain</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bis</LastName><ForeName>J C</ForeName><Initials>JC</Initials><AffiliationInfo><Affiliation>Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ikram</LastName><ForeName>M A</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>1] Department of Radiology and Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] The Netherlands Consortium of Healthy Aging, Leiden, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fornage</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Debette</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Launer</LastName><ForeName>L J</ForeName><Initials>LJ</Initials><AffiliationInfo><Affiliation>Laboratory of Neurogenetics, Intramural Research Program, National Institute of Aging, NIH, Bethesda, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Seshadri</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Erk</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>1] Department of Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany [2] Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, Berlin, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Walter</LastName><ForeName>H</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heinz</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bellivier</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stein</LastName><ForeName>J L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Medland</LastName><ForeName>S E</ForeName><Initials>SE</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Arias Vasquez</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hibar</LastName><ForeName>D P</ForeName><Initials>DP</Initials><AffiliationInfo><Affiliation>Imaging Genetics Center, Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Franke</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Martin</LastName><ForeName>N G</ForeName><Initials>NG</Initials><AffiliationInfo><Affiliation>Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wright</LastName><ForeName>M J</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>MooDS Bipolar Consortium</CollectiveName></Author><Author ValidYN="Y"><CollectiveName>Swedish Bipolar Study Group</CollectiveName></Author><Author ValidYN="Y"><CollectiveName>Alzheimer’s Disease Neuroimaging Initiative</CollectiveName></Author><Author ValidYN="Y"><CollectiveName>ENIGMA Consortium</CollectiveName></Author><Author ValidYN="Y"><CollectiveName>CHARGE Consortium</CollectiveName></Author><Author ValidYN="Y"><LastName>Su</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 NS017950</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U24 AG021886</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AG008122</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 HD050735</GrantID><Acronym>HD</Acronym><Agency>NICHD NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U01 AG049505</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>04</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Mol 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