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

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Version: Author's accepted manuscript
Serval ID
serval:BIB_0841E53F8F0F
Type
Article: article from journal or magazin.
Collection
Publications
Title
Meta-analysis of genome-wide association studies of anxiety disorders.
Journal
Molecular Psychiatry
Author(s)
Otowa T., Hek K., Lee M., Byrne E.M., Mirza S.S., Nivard M.G., Bigdeli T., Aggen S.H., Adkins D., Wolen A., Fanous A., Keller M.C., Castelao E., Kutalik Z., der Auwera S.V., Homuth G., Nauck M., Teumer A., Milaneschi Y., Hottenga J.J., Direk N., Hofman A., Uitterlinden A., Mulder C.L., Henders A.K., Medland S.E., Gordon S., Heath A.C., Madden P.A., Pergadia M.L., van der Most P.J., Nolte I.M., van Oort F.V., Hartman C.A., Oldehinkel A.J., Preisig M., Grabe H.J., Middeldorp C.M., Penninx B.W., Boomsma D., Martin N.G., Montgomery G., Maher B.S., van den Oord E.J., Wray N.R., Tiemeier H., Hettema J.M.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
21
Number
10
Pages
1391-1399
Language
english
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.Molecular Psychiatry advance online publication, 12 January 2016; doi:10.1038/mp.2015.197.
Pubmed
Create date
29/01/2016 12:26
Last modification date
20/08/2019 13:30
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