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

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. F., Pergadia, M. L., Van Der Most, P. J., Nolte, I. M., Van Oort, F. V. A., Hartman, C. A., Oldehinkel, A. J., Preisig, M., Grabe, H. J., Middeldorp, C. M., Penninx, B. W. J. H., Boomsma, D., Martin, N. G., Montgomery, G., Maher, B. S., Van Den Oord, E. J., Wray, N. R., Tiemeier, H. and Hettema, J. M. (2016) Meta-analysis of genome-wide association studies of anxiety disorders. Molecular Psychiatry, 21 10: 1391-1399. doi:10.1038/mp.2015.197

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Author 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. F.
Pergadia, M. L.
Van Der Most, P. J.
Nolte, I. M.
Van Oort, F. V. A.
Hartman, C. A.
Oldehinkel, A. J.
Preisig, M.
Grabe, H. J.
Middeldorp, C. M.
Penninx, B. W. J. H.
Boomsma, D.
Martin, N. G.
Montgomery, G.
Maher, B. S.
Van Den Oord, E. J.
Wray, N. R.
Tiemeier, H.
Hettema, J. M.
Title Meta-analysis of genome-wide association studies of anxiety disorders
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1476-5578
1359-4184
Publication date 2016-10-01
Year available 2016
Sub-type Article (original research)
DOI 10.1038/mp.2015.197
Open Access Status File (Author Post-print)
Volume 21
Issue 10
Start page 1391
End page 1399
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
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.
Formatted 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.
Keyword Biochemistry & Molecular Biology
Neurosciences
Psychiatry
Biochemistry & Molecular Biology
Neurosciences & Neurology
Psychiatry
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID RC2 MH089951
R01 MH061675
R01 MH087646
R01 AA007535
R01 AA014041
R01 MH081802
R01 MH066206
RC2 MH089995
U01 MH046276
R01 AA013326
R56 DA012854
R01 MH067257
R01 AA013321
230374
R01 MH060870
R01 MH059571
R01 MH059565
R01 MH059587
R01 DA012854
R01 MH059586
U01 MH046289
K08 DA019951
R01 MH059566
R01 MH059588
U01 MH046318
R01 MH060879
R01 AA013320
Institutional Status UQ

 
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