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Mol Psychiatry. 2016 Oct;21(10):1391-9. doi: 10.1038/mp.2015.197. Epub 2016 Jan 12.

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

Author information

1
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
2
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
3
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
4
Department of Psychiatry, Epidemiological and Social Psychiatric Research institute, Erasmus Medical Center, Rotterdam, The Netherlands.
5
QIMR Berghofer Institute of Medical Research, Brisbane, QLD, Australia.
6
Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
7
Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
8
Department of Pharmacy, Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, Richmond, VA, USA.
9
Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA.
10
Mental Health Service Line, Washington VA Medical Center, Washington DC, USA.
11
Department of Psychiatry, Georgetown University School of Medicine, Washington DC, USA.
12
Department of Psychology and Neuroscience, University of Colorado, Boulder, CO, USA.
13
Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.
14
Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
15
Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
16
Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
17
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
18
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
19
Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst Moritz Arndt-University Greifswald, Greifswald, Germany.
20
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
21
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
22
Department of Psychiatry, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
23
EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
24
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
25
Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
26
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
27
Florida Atlantic University, Boca Raton, FL, USA.
28
Department of Genetic Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
29
Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.
30
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
31
Department of Psychiatry and Psychotherapy, Helios Hospital Stralsund, Stralsund, Germany.
32
Department of Child and Adolescent Psychiatry, GGZ inGeest/VU University Medical Center, Amsterdam, The Netherlands.
33
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
34
Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.

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.

PMID:
26754954
PMCID:
PMC4940340
DOI:
10.1038/mp.2015.197
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no conflicts of interest.

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