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
26754954
TITLE
Meta-analysis of genome-wide association studies of anxiety disorders.
ABSTRACT
NlmCategory: UNASSIGNED
Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.Molecular Psychiatry advance online publication, 12 January 2016; doi:10.1038/mp.2015.197.
DATE PUBLISHED
2016 Jan 12
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2015/05/26
revised 2015/10/16
accepted 2015/11/05
entrez 2016/01/13 06:00
pubmed 2016/01/13 06:00
medline 2016/01/13 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Otowa T Otowa T T Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Hek K Hek K K Department of Psychiatry, Epidemiological and Social Psychiatric Research institute, Erasmus Medical Center, Rotterdam, The Netherlands.
Lee M Lee M M Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Byrne EM Byrne E M EM Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
Mirza SS Mirza S S SS Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Nivard MG Nivard M G MG Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
Bigdeli T Bigdeli T T Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Aggen SH Aggen S H SH Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Adkins D Adkins D D Department of Pharmacy, Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Wolen A Wolen A A Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA.
Fanous A Fanous A A Department of Psychiatry, Georgetown University School of Medicine, Washington DC, USA.
Keller MC Keller M C MC Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.
Castelao E Castelao E E Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
Kutalik Z Kutalik Z Z Swiss Institute of Bioinformatics, Lausanne, Switzerland.
der Auwera SV der Auwera S V SV Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Homuth G Homuth G G Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst Moritz Arndt-University Greifswald, Greifswald, Germany.
Nauck M Nauck M M Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Teumer A Teumer A A Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Milaneschi Y Milaneschi Y Y EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
Hottenga JJ Hottenga J-J JJ EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
Direk N Direk N N Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Hofman A Hofman A A Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Uitterlinden A Uitterlinden A A Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Mulder CL Mulder C L CL Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
Henders AK Henders A K AK Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
Medland SE Medland S E SE QIMR Berghofer Institute of Medical Research, Brisbane, QLD, Australia.
Gordon S Gordon S S QIMR Berghofer Institute of Medical Research, Brisbane, QLD, Australia.
Heath AC Heath A C AC Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Madden PA Madden P A F PA Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Pergadia ML Pergadia M L ML Florida Atlantic University, Boca Raton, FL, USA.
van der Most PJ van der Most P J PJ Department of Genetic Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Nolte IM Nolte I M IM Department of Genetic Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
van Oort FV van Oort F V A FV Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.
Hartman CA Hartman C A CA Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Oldehinkel AJ Oldehinkel A J AJ Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Preisig M Preisig M M Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
Grabe HJ Grabe H J HJ Department of Psychiatry and Psychotherapy, Helios Hospital Stralsund, Stralsund, Germany.
Middeldorp CM Middeldorp C M CM Department of Child and Adolescent Psychiatry, GGZ inGeest/VU University Medical Center, Amsterdam, The Netherlands.
Penninx BW Penninx B W J H BW EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
Boomsma D Boomsma D D EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
Martin NG Martin N G NG QIMR Berghofer Institute of Medical Research, Brisbane, QLD, Australia.
Montgomery G Montgomery G G QIMR Berghofer Institute of Medical Research, Brisbane, QLD, Australia.
Maher BS Maher B S BS Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
van den Oord EJ van den Oord E J EJ Department of Pharmacy, Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Wray NR Wray N R NR Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
Tiemeier H Tiemeier H H Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Hettema JM Hettema J M JM Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2016
MONTH: Jan
DAY: 12
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
COMMENTS AND CORRECTIONS
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GRANTID AGENCY COUNTRY
R01 MH087646 NIMH NIH HHS United States
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