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

被引：345

作者：

Otowa, T. ^{[1
,2
]}

Hek, K. ^{[3
,4
,5
]}

Lee, M. ^{[1
]}

Byrne, E. M. ^{[6
,7
]}

Mirza, S. S. ^{[3
]}

Nivard, M. G. ^{[8
]}

Bigdeli, T. ^{[1
]}

Aggen, S. H. ^{[1
]}

Adkins, D. ^{[9
]}

Wolen, A. ^{[10
]}

Fanous, A. ^{[11
,12
]}

Keller, M. C. ^{[13
,14
]}

Castelao, E. ^{[15
]}

Kutalik, Z. ^{[16
,17
,18
]}

der Auwera, S. V. ^{[19
]}

Homuth, G. ^{[20
,21
]}

Nauck, M. ^{[22
]}

Teumer, A. ^{[23
]}

Milaneschi, Y. ^{[24
,25
]}

Hottenga, J-J ^{[24
,25
]}

Direk, N. ^{[3
]}

Hofman, A. ^{[3
]}

Uitterlinden, A. ^{[3
,26
]}

Mulder, C. L. ^{[27
]}

Henders, A. K. ^{[6
,7
]}

Medland, S. E. ^{[6
]}

Gordon, S. ^{[6
]}

Heath, A. C. ^{[28
]}

Madden, P. A. F. ^{[28
]}

Pergadia, M. L. ^{[28
,29
]}

van der Most, P. J. ^{[30
]}

Nolte, I. M. ^{[30
]}

van Oort, F. V. A. ^{[31
]}

Hartman, C. A. ^{[32
]}

Oldehinkel, A. J. ^{[32
]}

Preisig, M. ^{[15
]}

Grabe, H. J. ^{[19
,33
]}

Middeldorp, C. M. ^{[8
,34
]}

Penninx, B. W. J. H. ^{[24
,25
]}

Boomsma, D. ^{[8
,25
]}

Martin, N. G. ^{[6
]}

Montgomery, G. ^{[6
]}

Maher, B. S. ^{[35
]}

van den Oord, E. J. ^{[9
]}

Wray, N. R. ^{[6
,7
]}

Tiemeier, H. ^{[3
,27
,36
]}

Hettema, J. M. ^{[1
]}

机构：

[1] Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, POB 980126, Richmond, VA 23298 USA

[2] Univ Tokyo, Dept Neuropsychiat, Grad Sch Med, Tokyo, Japan

[3] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[4] Erasmus MC, Dept Psychiat Epidemiol, Rotterdam, Netherlands

[5] Erasmus MC, Social Psychiat Res Inst, Rotterdam, Netherlands

[6] QIMR Berghofer Inst Med Res, Brisbane, Qld, Australia

[7] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[8] Vrije Univ Amsterdam, Biol Psychol, Amsterdam, Netherlands

[9] Virginia Commonwealth Univ, Ctr Biomarker Res & Personalized Med, Dept Pharm, Richmond, VA USA

[10] Virginia Commonwealth Univ, Ctr Clin & Translat Res, Richmond, VA USA

[11] Washington VA Med Ctr, Mental Hlth Serv Line, Washington, DC USA

[12] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA

[13] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA

[14] Univ Colorado, Inst Behav Genet, Boulder, CO USA

[15] Univ Lausanne Hosp, Dept Psychiat, Lausanne, Switzerland

[16] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland

[17] CHU Vaudois, Inst Social & Prevent Med, Lausanne, Switzerland

[18] Swiss Inst Bioinformat, Lausanne, Switzerland

[19] Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany

[20] Univ Med, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[21] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany

[22] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany

[23] Univ Med Greifswald, Inst Community Med, Greifswald, Germany

[24] Vrije Univ Amsterdam, GGZ inGeest, Dept Psychiat, Med Ctr, Amsterdam, Netherlands

[25] Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, Med Ctr, Amsterdam, Netherlands

[26] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[27] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands

[28] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[29] Florida Atlantic Univ, Boca Raton, FL USA

[30] Univ Groningen, Univ Med Ctr Groningen, Dept Genet Epidemiol, Groningen, Netherlands

[31] Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands

[32] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands

[33] Helios Hosp Stralsund, Dept Psychiat & Psychotherapy, Stralsund, Germany

[34] GGZ inGeest VU Univ, Med Ctr, Dept Child & Adolescent Psychiat, Amsterdam, Netherlands

[35] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA

[36] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands

来源：

MOLECULAR PSYCHIATRY | 2016年 / 21卷 / 10期

基金：

日本学术振兴会;

关键词：

ENVIRONMENTAL RISK-FACTORS; NETHERLANDS TWIN REGISTER; GENETIC EPIDEMIOLOGY; LIFETIME PREVALENCE; DEPRESSION; POLYGENICITY; OBJECTIVES; MORBIDITY; SAMPLE; POWER;

D O I：

10.1038/mp.2015.197

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 x 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P = 2.86 x 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.

引用

页码：1391 / 1399

页数：9

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