Replication and meta-analysis of TMEM132D gene variants in panic disorder

被引：63

作者：

Erhardt, A. ^{[1
]}

Akula, N. ^{[2
]}

Schumacher, J. ^{[3
]}

Czamara, D. ^{[1
]}

Karbalai, N. ^{[1
]}

Mueller-Myhsok, B. ^{[1
]}

Mors, O. ^{[4
]}

Borglum, A. ^{[5
]}

Kristensen, A. S. ^{[4
]}

Woldbye, D. P. D. ^{[6
]}

Koefoed, P. ^{[6
]}

Eriksson, E. ^{[7
]}

Maron, E.

Metspalu, A. ^{[8
,9
]}

Nurnberger, J. ^{[10
]}

Philibert, R. A. ^{[11
]}

Kennedy, J. ^{[12
]}

Domschke, K. ^{[13
]}

Reif, A. ^{[13
]}

Deckert, J. ^{[13
]}

Otowa, T. ^{[14
]}

Kawamura, Y. ^{[15
]}

Kaiya, H. ^{[16
,17
]}

Okazaki, Y. ^{[18
]}

Tanii, H. ^{[19
]}

Tokunaga, K. ^{[20
]}

Sasaki, T. ^{[21
]}

Ioannidis, J. P. A. ^{[22
,23
,24
]}

McMahon, F. J. ^{[2
]}

Binder, E. B. ^{[1
]}

机构：

[1] Max Planck Inst Psychiat, D-80804 Munich, Germany

[2] NIMH, Human Genet Branch, Intramural Res Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[3] Univ Bonn, Inst Human Genet, Bonn, Germany

[4] Aarhus Univ, Dept Psychiat, Aarhus, Denmark

[5] Aarhus Univ, Dept Biomed, Aarhus, Denmark

[6] Univ Copenhagen, Dept Neurosci & Pharmacol, Copenhagen, Denmark

[7] Univ Gothenburg, Gothenburg, Sweden

[8] Univ Tartu, Inst Mol & Cell Biol, Estonian Genome Ctr, EE-50090 Tartu, Estonia

[9] Estonian Bioctr, Tartu, Estonia

[10] Indiana Univ, Dept Psychiat, Indianapolis, IN 46204 USA

[11] Univ Iowa, Iowa City, IA USA

[12] Univ Toronto, Toronto, ON, Canada

[13] Univ Wurzburg, Dept Psychiat, D-8700 Wurzburg, Germany

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

[15] Nagoya Mental Clin, Res Ctr Pan Disorder, Nagoya, Aichi, Japan

[16] Akasaka Mental Clin, Tokyo, Japan

[17] Res Ctr PanIC Disorder, Nagoya, Aichi, Japan

[18] Tokyo Metropolitan Matsuzawa Hosp, Dept Neurol, Tokyo, Japan

[19] Mie Univ, Grad Sch Med, Dept Neuropsychiat, Tsu, Mie, Japan

[20] Univ Tokyo, Grad Sch Med, Dept Human Genet, Tokyo, Japan

[21] Univ Tokyo, Grad Sch Educ, Lab Hlth Educ, Tokyo, Japan

[22] Stanford Univ, Stanford Prevent Res Ctr, Dept Hlth Res & Policy, Stanford, CA 94305 USA

[23] Stanford Univ, Stanford Prevent Res Ctr, Dept Stat, Stanford, CA 94305 USA

[24] Stanford Univ, Stanford Prevent Res Ctr, Dept Med, Stanford, CA 94305 USA

来源：

TRANSLATIONAL PSYCHIATRY | 2012年 / 2卷

关键词：

GENOME-WIDE ASSOCIATION;

D O I：

10.1038/tp.2012.85

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

A recent genome-wide association study in patients with panic disorder (PD) identified a risk haplotype consisting of two single-nucleotide polymorphisms (SNPs) (rs7309727 and rs11060369) located in intron 3 of TMEM132D to be associated with PD in three independent samples. Now we report a subsequent confirmation study using five additional PD case-control samples (n = 1670 cases and n 2266 controls) assembled as part of the Panic Disorder International Consortium (PanIC) study for a total of 2678 cases and 3262 controls in the analysis. In the new independent samples of European ancestry (EA), the association of rs7309727 and the risk haplotype rs7309727-rs11060369 was, indeed, replicated, with the strongest signal coming from patients with primary PD, that is, patients without major psychiatric comorbidities (n 1038 cases and n 2411 controls). This finding was paralleled by the results of the meta-analysis across all samples, in which the risk haplotype and rs7309727 reached P-levels of P = 1.4e-8 and P = 1.1e-8, respectively, when restricting the samples to individuals of EA with primary PD. In the Japanese sample no associations with PD could be found. The present results support the initial finding that TMEM132D gene contributes to genetic susceptibility for PD in individuals of EA. Our results also indicate that patient ascertainment and genetic background could be important sources of heterogeneity modifying this association signal in different populations. Translational Psychiatry (2012) 2, e156; doi:10.1038/tp.2012.85; published online 4 September 2012

引用

页码：e156 / e156

页数：6

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