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The norepinephrine transporter gene is a candidate gene for panic disorder

  • Biological Psychiatry - Original Article
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Abstract

Panic disorder (PD) is an anxiety disorder characterized by recurrent panic attacks with a lifetime prevalence of 4.7%. Genetic factors are known to contribute to the development of the disorder. Several lines of evidence point towards a major role of the norepinephrine system in the pathogenesis of PD. The SLC6A2 gene is located on chromosome 16q12.2 and encodes the norepinephrine transporter (NET), responsible for the reuptake of norepinephrine into presynaptic nerve terminals. The aim of the present study was to analyze genetic variants located within the NET gene for association with PD. The case–control sample consisted of 449 patients with PD and 279 ethnically matched controls. All cases fulfilled the ICD-10 diagnostic criteria for PD. Genotyping was performed using the Sequenom platform (Sequenom, Inc, San Diego, USA). To test for allelic and haplotypic association, the PLINK software was used, and COMBASSOC was applied to test for gene-wise association. After quality control 29 single nucleotide polymorphisms (SNPs) spanning the gene-region were successfully analyzed. Seven SNPs located within the 5′ end of the gene were significantly associated with PD. Furthermore, the NET gene showed overall evidence for association with the disease (P = 0.000035). In conclusion, the present study indicates that NET could be a susceptibility gene for PD.

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Acknowledgments

The authors acknowledge Karina Birk Nygaard, Tracey Flint and Mia Boe Oddershede for excellent technical assistance. The study was supported by the Lundbeck foundation, “TRYG fonden”, “Forskningsfonden til støtte af psykiatrisk forskning i Region Midtjylland”, “Toyota fonden”, Denmark, and the Villum Kann Rasmussen Foundation.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Skovagervej 2, 8240, Risskov, Denmark

    H. N. Buttenschøn, A. S. Kristensen, H. N. Buch, A. D. Børglum & O. Mors

  2. Department of Occupational Medicine, Danish Ramazzini Centre, Regional Hospital Herning, Herning, Denmark

    J. H. Andersen & A. Kaergaard

  3. Department of Occupational Medicine, Bispebjerg University Hospital, Copenhagen, Denmark

    J. P. Bonde, S. Mikkelsen & J. F. Thomsen

  4. Department of Occupational Medicine, Danish Ramazzini Centre, Aarhus University Hospital, Aarhus, Denmark

    M. Grynderup, H. Kolstad & L. Kaerlev

  5. National Research Centre for the Work Environment, Copenhagen, Denmark

    A. M. Hansen

  6. Center for National Clinical Databases South, Odense University Hospital, Odense, Denmark

    L. Kaerlev

  7. Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen and Psychiatric Centre Copenhagen, Copenhagen, Denmark

    P. Koefoed & D. P. D. Woldbye

  8. Max Planck Institute of Psychiatry, Munich, Germany

    A. Erhardt

  9. Department of Human Genetics, Aarhus University, Aarhus, Denmark

    A. D. Børglum

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  1. H. N. Buttenschøn
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  9. A. Kaergaard
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  10. L. Kaerlev
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  11. S. Mikkelsen
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  12. J. F. Thomsen
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  13. P. Koefoed
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  14. A. Erhardt
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  15. D. P. D. Woldbye
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Correspondence to H. N. Buttenschøn.

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Buttenschøn, H.N., Kristensen, A.S., Buch, H.N. et al. The norepinephrine transporter gene is a candidate gene for panic disorder. J Neural Transm 118, 969–976 (2011). https://doi.org/10.1007/s00702-011-0624-7

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  • DOI: https://doi.org/10.1007/s00702-011-0624-7

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