Evidence map›Paper›PMID 26754954›Full record

SynthesisMolecular psychiatry2016

Meta-analysis of genome-wide association studies of anxiety disorders.

T Otowa, K Hek, M Lee, E M Byrne, S S Mirza, M G Nivard, T Bigdeli, S H Aggen, D Adkins, A Wolen and 37 more

Erratum issuedAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 263 papers, 15 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
263citing papers in PubMed, 15 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

263 citing papers in PubMed, 15 syntheses or guidelines pooled it.

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  10. Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms.Journal of the American Academy of Child and Adolescent Psychiatry · 2022
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203 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

47 authors.

T OtowaDepartment of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
K HekDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
M LeeDepartment of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
E M ByrneQIMR Berghofer Institute of Medical Research, Brisbane, QLD, Australia.
S S MirzaDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
M G NivardBiological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
T BigdeliDepartment of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
S H AggenDepartment of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
D AdkinsDepartment of Pharmacy, Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, Richmond, VA, USA.
A WolenCenter for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA.ORCID 0000-0003-2542-2202
A FanousMental Health Service Line, Washington VA Medical Center, Washington DC, USA.
M C KellerDepartment of Psychology and Neuroscience, University of Colorado, Boulder, CO, USA.
E CastelaoDepartment of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
Z KutalikDepartment of Medical Genetics, University of Lausanne, Lausanne, Switzerland.ORCID 0000-0001-8285-7523
S Van der AuweraDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
G HomuthInterfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst Moritz Arndt-University Greifswald, Greifswald, Germany.
M NauckInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
A TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.ORCID 0000-0002-8309-094X
Y MilaneschiDepartment of Psychiatry, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
J-J HottengaDepartment of Psychiatry, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
N DirekDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
A HofmanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
A UitterlindenDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
C L MulderDepartment of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
A K HendersQIMR Berghofer Institute of Medical Research, Brisbane, QLD, Australia.
S E MedlandQIMR Berghofer Institute of Medical Research, Brisbane, QLD, Australia.
S GordonQIMR Berghofer Institute of Medical Research, Brisbane, QLD, Australia.
A C HeathDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
P A F MaddenDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
M L PergadiaDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
P J van der MostDepartment of Genetic Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
I M NolteDepartment of Genetic Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
F V A van OortDepartment of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.
C A HartmanDepartment of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
A J OldehinkelDepartment of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
M PreisigDepartment of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
H J GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
C M MiddeldorpBiological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
B W J H PenninxDepartment of Psychiatry, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
D BoomsmaBiological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
N G MartinQIMR Berghofer Institute of Medical Research, Brisbane, QLD, Australia.
G MontgomeryQIMR Berghofer Institute of Medical Research, Brisbane, QLD, Australia.
B S MaherDepartment of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
E J van den OordDepartment of Pharmacy, Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, Richmond, VA, USA.
N R WrayQIMR Berghofer Institute of Medical Research, Brisbane, QLD, Australia.
H TiemeierDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.ORCID 0000-0002-4395-1397
J M HettemaDepartment of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.

Funding

THE GENETICS OF VULNERABILITY TO NICOTINE ADDICTIONSR01DA012854 · NIDA · WASHINGTON UNIVERSITY · PI MADDEN, PAMELA ANN · 2000 to 2013
$10.4M
MOLECULAR GENETICS OF SCHIZOPHRENIAR01MH059571 · NIMH · UNIVERSITY OF CHICAGO · PI GEJMAN, PABLO V. · 1999 to 2007
$8.0M
Integration of Genomics & Transcriptomics in Normal Twins & Major DepressionRC2MH089951 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SULLIVAN, PATRICK F · 2009 to 2010
$6.5M
Estimating the genetic and environmental architecture of psychiatric disordersR01MH100141 · NIMH · UNIVERSITY OF COLORADO · PI KELLER, MATTHEW CHARLES · 2013 to 2022
$5.3M
Molecular Epidemiology of Alcoholism 3 - EDAC FamiliesR01AA013321 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 2001 to 2005
$4.3M
Genomics of Developmental Trajectories in TwinsRC2MH089995 · NIMH · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI HUDZIAK, JAMES J. · 2009 to 2010
$3.8M
Molecular Epidemiology of Alcoholism 2- Big SibshipsR01AA013320 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 2003 to 2007
$3.1M
MOLECULAR GENETICS OF SCHIZOPHRENIAR01MH060879 · NIMH · WASHINGTON UNIVERSITY · PI CLONINGER, C. ROBERT · 1999 to 2006
$2.7M
Genetic Epidemiology of Pathological GamblingR01MH066206 · NIMH · UNIVERSITY OF MISSOURI-COLUMBIA · PI SLUTSKE, WENDY S · 2003 to 2007
$2.5M
Molecular Epidemiology of Alcoholism 1: Candidate GeneR01AA013326 · NIAAA · QUEENSLAND INSTITUTE OF MEDICAL RESEARCH · PI MARTIN, NICHOLAS G · 2001 to 2005
$2.1M
VARIATION IN THE EFFECTS OF ALCOHOL ON LIVER FUNCTIONR01AA014041 · NIAAA · QUEENSLAND INSTITUTE OF MEDICAL RESEARCH · PI WHITFIELD, JOHN B · 2003 to 2007
$2.1M
MOLECULAR GENETICS OF SCHIZOPHRENIAR01MH059586 · NIMH · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SILVERMAN, JEREMY M. · 1999 to 2006
$1.9M
European Research Council 230374NIAAA NIH HHS R01 AA007535NIAAA NIH HHS R01 AA013320NIAAA NIH HHS R01 AA013321NIAAA NIH HHS R01 AA013326NIAAA NIH HHS R01 AA014041NIDA NIH HHS K08 DA019951NIDA NIH HHS R01 DA012854NIDA NIH HHS R56 DA012854NIMH NIH HHS R01 MH059565NIMH NIH HHS R01 MH059566NIMH NIH HHS R01 MH059571NIMH NIH HHS R01 MH059586NIMH NIH HHS R01 MH059587NIMH NIH HHS R01 MH059588NIMH NIH HHS R01 MH060870NIMH NIH HHS R01 MH060879NIMH NIH HHS R01 MH061675NIMH NIH HHS R01 MH066206NIMH NIH HHS R01 MH067257NIMH NIH HHS R01 MH081802NIMH NIH HHS R01 MH087646NIMH NIH HHS R01 MH100141NIMH NIH HHS RC2 MH089951NIMH NIH HHS RC2 MH089995NIMH NIH HHS U01 MH046276NIMH NIH HHS U01 MH046289NIMH NIH HHS U01 MH046318
6 · The paper itself

Abstract

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.

Indexed as

Anxiety DisordersCase-Control StudiesGenetic Association StudiesGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyGenotypeHumansPolymorphism, Single NucleotideRisk FactorsWhite People

Identifiers

PMID26754954
PMCPMC4940340

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.