Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways

doi:10.1038/mp.2015.138

Review

. 2016 May;21(5):665-79.

doi: 10.1038/mp.2015.138. Epub 2015 Sep 22.

Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways

A S Howe¹, H N Buttenschøn^{2

3}, A Bani-Fatemi¹, E Maron^{4

5}, T Otowa⁶, A Erhardt⁷, E B Binder⁷, N O Gregersen^{2

3}, O Mors^{3

8}, D P Woldbye⁹, K Domschke¹⁰, A Reif¹¹, J Shlik¹², S Kõks¹³, Y Kawamura¹⁴, A Miyashita¹⁴, R Kuwano¹⁵, K Tokunaga¹⁶, H Tanii¹⁷, J W Smoller¹⁸, T Sasaki¹⁹, D Koszycki^{20

21

22}, V De Luca^{1

23}

Affiliations

¹ Neurogenetics Department, Centre for Addiction and Mental Health, Toronto, ON, Canada.
² Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark.
³ The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark.
⁴ Department of Neuropsychopharmacology and Molecular Imaging, Imperial College London, London, UK.
⁵ Department of Psychiatry, University of Tartu, Tartu, Estonia.
⁶ Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
⁷ Max Planck Institute of Psychiatry, Munich, Germany.
⁸ Research Department P, Aarhus University Hospital, Risskov, Denmark.
⁹ Laboratory of Neuroplasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
¹¹ Department of Psychiatry, Psychosomatics and Psychotherapy, Goethe-University Frankfurt, Frankfurt am Main, Germany.
¹² Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada.
¹³ Department of Physiology, University of Tartu, Tartu, Estonia.
¹⁴ Department of Psychiatry, Sakae Seijinkai Hospital, Yokohama, Kanagawa, Japan.
¹⁵ Department of Molecular Genetics, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan.
¹⁶ Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
¹⁷ Department of Psychiatry, Division of Neuroscience, Graduate School of Medicine, Brain Science and Animal Model Research Center, Mie University, Tsu, Japan.
¹⁸ Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
¹⁹ Laboratory of Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan.
²⁰ Faculty of Education (Counselling), University of Ottawa, Ottawa, ON, Canada.
²¹ Faculty of Medicine (Psychiatry), University of Ottawa, Ottawa, Ontario, Canada.
²² Institut de Recherche de l'Hôpital Montfort, Ottawa, ON, Canada.
²³ Department of Psychiatry, Centre for Addiction and Mental Health, Toronto, Canada.

PMID: 26390831
DOI: 10.1038/mp.2015.138

Review

Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways

A S Howe et al. Mol Psychiatry. 2016 May.

. 2016 May;21(5):665-79.

doi: 10.1038/mp.2015.138. Epub 2015 Sep 22.

Authors

Affiliations

¹ Neurogenetics Department, Centre for Addiction and Mental Health, Toronto, ON, Canada.
² Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark.
³ The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark.
⁴ Department of Neuropsychopharmacology and Molecular Imaging, Imperial College London, London, UK.
⁵ Department of Psychiatry, University of Tartu, Tartu, Estonia.
⁶ Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
⁷ Max Planck Institute of Psychiatry, Munich, Germany.
⁸ Research Department P, Aarhus University Hospital, Risskov, Denmark.
⁹ Laboratory of Neuroplasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
¹¹ Department of Psychiatry, Psychosomatics and Psychotherapy, Goethe-University Frankfurt, Frankfurt am Main, Germany.
¹² Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada.
¹³ Department of Physiology, University of Tartu, Tartu, Estonia.
¹⁴ Department of Psychiatry, Sakae Seijinkai Hospital, Yokohama, Kanagawa, Japan.
¹⁵ Department of Molecular Genetics, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan.
¹⁶ Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
¹⁷ Department of Psychiatry, Division of Neuroscience, Graduate School of Medicine, Brain Science and Animal Model Research Center, Mie University, Tsu, Japan.
¹⁸ Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
¹⁹ Laboratory of Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan.
²⁰ Faculty of Education (Counselling), University of Ottawa, Ottawa, ON, Canada.
²¹ Faculty of Medicine (Psychiatry), University of Ottawa, Ottawa, Ontario, Canada.
²² Institut de Recherche de l'Hôpital Montfort, Ottawa, ON, Canada.
²³ Department of Psychiatry, Centre for Addiction and Mental Health, Toronto, Canada.

PMID: 26390831
DOI: 10.1038/mp.2015.138

Abstract

The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered association studies and ancestry-specific effects. In the present study, we performed a succinct review of case-control association studies published prior to April 2015. Meta-analyses were performed for candidate gene variants examined in at least three studies using the Cochrane Mantel-Haenszel fixed-effect model. Secondary analyses were also performed to assess the influences of sex, agoraphobia co-morbidity and ancestry-specific effects on panicogenesis. Meta-analyses were performed on 23 variants in 20 PD candidate genes. Significant associations after correction for multiple testing were observed for three variants, TMEM132D rs7370927 (T allele: odds ratio (OR)=1.27, 95% confidence interval (CI): 1.15-1.40, P=2.49 × 10(-6)), rs11060369 (CC genotype: OR=0.65, 95% CI: 0.53-0.79, P=1.81 × 10(-5)) and COMT rs4680 (Val (G) allele: OR=1.27, 95% CI: 1.14-1.42, P=2.49 × 10(-5)) in studies with samples of European ancestry. Nominal associations that did not survive correction for multiple testing were observed for NPSR1 rs324891 (T allele: OR=1.22, 95% CI: 1.07-1.38, P=0.002), TPH1 rs1800532 (AA genotype: OR=1.46, 95% CI: 1.14-1.89, P=0.003) and HTR2A rs6313 (T allele: OR=1.19, 95% CI: 1.07-1.33, P=0.002) in studies with samples of European ancestry and for MAOA-uVNTR in female PD (low-active alleles: OR=1.21, 95% CI: 1.07-1.38, P=0.004). No significant associations were observed in the secondary analyses considering sex, agoraphobia co-morbidity and studies with samples of Asian ancestry. Although these findings highlight a few associations, PD likely involves genetic variation in a multitude of biological pathways that is diverse among populations. Future studies must incorporate larger sample sizes and genome-wide approaches to further quantify the observed genetic variation among populations and subphenotypes of PD.

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[1] Psychiatry Res. 2010 Aug 30;179(1):119-20 - PubMed

[2] Psychiatry Res. 2010 Aug 30;179(1):119-20 - PubMed

[3] Hum Mol Genet. 1999 Apr;8(4):621-4 - PubMed

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[9] Res Synth Methods. 2010 Apr;1(2):97-111 - PubMed

[10] Res Synth Methods. 2010 Apr;1(2):97-111 - PubMed

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Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways

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Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways

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