Association study of 90 candidate gene polymorphisms in panic disorder
Abstract
OBJECTIVE: In the present investigation we screened a large number of single nucleotide polymorphisms in the genes relevant to the neurobiology of anxiety for their association with panic disorder (PD). METHODS: The study sample included 127 patients with PD and 146 healthy control subjects. Using Arrayed Primer Extension technology we genotyped 90 polymorphisms in 21 candidate genes of serotonin, cholecystokinin, dopamine and opioid neurotransmitter systems. The association and haplotype analyses were performed in the whole group (PD-all) and in the subgroups of PD comorbid with major depression (PD-comorbid, n = 60) and without any comorbidity (PD-pure, n = 42). RESULTS: From the set of 90 polymorphisms, eight single nucleotide polymorphism markers in eight genes displayed at least a nominal association with any of the studied PD phenotype subgroups. Several polymorphisms of cholecystokinin, serotonin and dopamine systems were associated with PD-all and/or PD-comorbid phenotypes, while pure PD was associated only with HTR2A receptor 102T-C (P = 0.01) and DRD1 receptor -94G-A (P = 0.02) polymorphisms. Haplotype analysis supported an association of the cholecystokinin gene TG haplotype with the PD-all group (P = 0.04), whereas DRD1 receptor CAA and HTR2A receptor AT haplotypes were associated with a lower risk for PD-pure phenotype (P = 0.03 and P = 0.04, respectively). CONCLUSIONS: The study results suggest that genetic variants of several candidate genes of neurotransmitter systems, each of a minor individual effect, may contribute to the susceptibility to PD. Our data also indicate that genetic variability may have a distinctive influence on pure and comorbid phenotypes of PD.
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Direct implications were demonstrated for the monoamine oxidase A, 5-hydroxytryptamine transporter, and catechol-O-methyltransferase genes in BD.
“In this way, direct implications were demonstrated for the monoamine oxidase A, 5-hydroxytryptamine transporter, and catechol-O-methyltransferase genes [217–220].”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [217]
Cites
(1998) · The Journal of Clinical Psychiatry · Cited by 19,139 · see citing works
GENEPOP (version 1.2): population genetic software for exact tests and ecumenicism
Raymond, M., & Rousset, F. (1995) · Journal of Heredity · doi:10.1093/oxfordjournals.jhered.a111573 · Cited by 16,187 · see citing works
The mini international neuropsychiatric interview
Lecrubier, Y., Sheehan, D. V., Hergueta, T., & Weiller, E. (1998) · European Psychiatry · doi:10.1016/s0924-9338(99)80239-9 · Cited by 5,882 · see citing works
Neuroanatomical Hypothesis of Panic Disorder, Revised
Gorman, J. M., KENT, J. M., Sullivan, G. M., & Coplan, J. D. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.4.493 · Cited by 998 · see citing works
D1 receptors in prefrontal cells and circuits
Goldman-Rakic, P. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(99)00045-4 · Cited by 807 · see citing works
Lemonde, S., Turecki, G., Bakish, D., Du, L., Hrdina, P. D., Bown, C. D., Sequeira, A., Kushwaha, N., Morris, S. J., Basak, A., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-25-08788.2003 · Cited by 733 · see citing works
Deckert, J., Catalano, M., Syagailo, Y. V., Bosi, M., Okladnova, O., Di Bella, D., Nothen, M. M., Maffei, P., Franke, P., Fritze, J., et al. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.4.621 · Cited by 582 · see citing works
Panic and panic disorder in the United States
Eaton, W. W., Kessler, R. C., Wïttchen, H., & Magee, W. J. (1994) · American Journal of Psychiatry · doi:10.1176/ajp.151.3.413 · Cited by 376 · see citing works
Kessler, R. C., Stang, P., Wittchen, H., Üstün, T. B., Roy-Burne, P. P., & Walters, E. (1998) · The British journal of psychiatry : the journal of mental science · doi:10.1001/archpsyc.55.9.801 · Cited by 357 · see citing works
Relationship Between Panic Disorder and Agoraphobia
Noyes, R. (1986) · Archives of General Psychiatry · doi:10.1001/archpsyc.1986.01800030037004 · Cited by 295 · see citing works
Roth, B. L. (1998) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(98)00019-9 · Cited by 283 · see citing works
Summerly, R., & DONALDSON, E. M. (1962) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1962.tb13432.x · Cited by 270 · see citing works
Meta-analysis of studies on genetic variation in 5-HT2A receptors and clozapine response
Arranz, M. J., Munro, J., Sham, P. C., Kirov, G., Murray, R. M., Collier, D. A., & Kerwin, R. W. (1998) · Schizophrenia Research · doi:10.1016/s0920-9964(98)00032-2 · Cited by 255 · see citing works
Williams, J. H., Spurlock, G., McGuffin, P., Owen, M., Mallet, J. J., Nöthen, M. M., Gill, M., Aschauer, H. N., Nylander, P.-O., & Macciardi, F. M. (1996) · The Lancet · doi:10.1016/s0140-6736(96)90939-3 · Cited by 245 · see citing works
Chen, Y. W., & Dilsaver, S. C. (1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.2.280 · Cited by 220 · see citing works
Panic disorder in women: a population-based twin study
Kendler, K. S., Neale, M. C., Kessler, R. C., Heath, A. C., & Eaves, L. J. (1993) · Psychological Medicine · doi:10.1017/s003329170002849x · Cited by 197 · see citing works
Specific haplotypes of the P-selectin gene are associated with myocardial infarction
Trégouët, D. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.17.2015 · Cited by 177 · see citing works
Deckert, J., Nöthen, M. M., Franke, P. E., Delmo, C. D., Fritze, J., Knapp, M., Maier, W., Beckmann, H., & Propping, P. (1998) · Molecular Psychiatry · doi:10.1038/sj.mp.4000345 · Cited by 162 · see citing works
Lerer, B., Macciardi, F. M., Segman, R. H., Adolfsson, R., Blackwood, D., Blairy, S., Del‐Favero, J., Dikeos, D. G., Kaneva, R. P., Lilli, R., et al. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000883 · Cited by 160 · see citing works
Neurobiology of panic disorder
Bourin, M., Baker, G. B., & Bradwejn, J. (1998) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(97)00203-1 · Cited by 155 · see citing works
Investigation of cholecystokinin system genes in panic disorder
Kennedy, J. L., Bradwejn, J., Koszycki, D., King, N. A., Crowe, R., Vincent, J. B., & Fourie, O. (1999) · Molecular Psychiatry · doi:10.1038/sj.mp.4000507 · Cited by 126 · see citing works
A controlled family study in panic disorder
Maier, W., Lichtermann, D., Minges, J., Oehrlein, A., & Franke, P. E. (1993) · Journal of Psychiatric Research · doi:10.1016/0022-3956(93)90019-x · Cited by 125 · see citing works
Rothe, C., Gutknecht, L., Freitag, C. M., Tauber, R., Mößner, R., Franke, P. E., Fritze, J., Wagner, G., Peikert, G., Wenda, B., et al. (2004) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145703004061 · Cited by 123 · see citing works
Tadić, A., Rujescu, D., Szegedi, A., Giegling, I., SINGER, P. A., Möller, H. ‐., & Dahmen, N. (2002) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.10013 · Cited by 116 · see citing works
Functional promoter polymorphism of the human serotonin transporter
Deckert, J., Catalano, M., Heils, A., Bella, D. D., Friess, F., Politi, E., Franke, P. E., Nöthen, M. M., Maier, W., Bellodi, L., et al. (1997) · Psychiatric Genetics · doi:10.1097/00041444-199700710-00008 · Cited by 108 · see citing works
No association between anxiety disorders and catechol-O-methyltransferase polymorphism
Ohara, K., Nagai, M., Suzuki, Y., Ochiai, M., & Ohara, K. (1998) · Psychiatry Research · doi:10.1016/s0165-1781(98)00062-6 · Cited by 105 · see citing works
Cusin, C., Serretti, A., Zanardi, R., Lattuada, E., Rossini, D., Lilli, R., Lorenzi, C., & Smeraldi, E. (2002) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145701002711 · Cited by 101 · see citing works
Catechol O-Methyltransferase Genetic Polymorphism in Panic Disorder
Woo, J., Yoon, K., & Yu, B. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.10.1785 · Cited by 101 · see citing works
Evaluating the arrayed primer extension resequencing assay of TP53 tumor suppressor gene
Tõnisson, N., Zernant, J., Kurg, A., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082100599 · Cited by 97 · see citing works
Self-citationSearch for association between suicide attempt and serotonergic polymorphisms
Geijer, T., Frisch, A., Persson, M.-L., Wasserman, D., Rockah, R., Michaelovsky, E., Apter, A. S., Jönsson, E. G., Nöthen, M. M., & Weizman, A. (2000) · Psychiatric Genetics · doi:10.1097/00041444-200010010-00004 · Cited by 96 · see citing works
Costs and Offset Effect in Panic Disorders
Salvador‐Carulla, L., Seguı́, J., Fernández-Cano, P., & Canet, J. (1995) · The British Journal of Psychiatry · doi:10.1192/s0007125000293367 · Cited by 93 · see citing works
Panic, Agoraphobia, and Panic Disorder with Agoraphobia
Goisman, R. M., Warshaw, M. G., Peterson, L. G., Rogers, M. P., CUNEO, P., HUNT, M. F., TOMLIN-ALBANESE, J. M., Kazim, A., Gollan, J. K., EPSTEIN-KAYE, T., et al. (1994) · The Journal of Nervous and Mental Disease · doi:10.1097/00005053-199402000-00002 · Cited by 91 · see citing works
Han, L., Nielsen, D. A., Rosenthal, N. E., Jefferson, K., Kaye, W. H., Murphy, D. L., Altemus, M., Humphries, J. R., Cassano, G. B., Rotondo, A., et al. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00122-x · Cited by 89 · see citing works
Schizophrenia and smoking: Evidence for a common neurobiological basis?
Stassen, H. H., Bridler, R., H�gele, S., Hergersberg, M., Mehmann, B., Schinzel, A., Weisbrod, M., & Scharfetter, C. (2000) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(20000403)96:2 · Cited by 89 · see citing works
Positive association between panic disorder and polymorphism of the serotonin 2A receptor gene
Inada, Y., Yoneda, H., Koh, J., Sakai, J., Himei, A., Kinoshita, Y., Akabame, K., Hiraoka, Y., & Sakai, T. (2003) · Psychiatry Research · doi:10.1016/s0165-1781(03)00064-7 · Cited by 85 · see citing works
Fehr, C., Grintschuk, N., Szegedi, A., Anghelescu, I. G., Klawe, C., SINGER, P. A., Hiemke, C., & Dahmen, N. (2000) · Psychiatry Research · doi:10.1016/s0165-1781(00)00215-8 · Cited by 76 · see citing works
Panic disorder in the general medical setting
Zaubler, T. S., & Katon, W. J. (1998) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(97)00134-7 · Cited by 74 · see citing works
Hamilton, S. P., Heiman, G. A., Haghighi, F. G., Mick, S., Klein, D. F., Hodge, S. E., Weissman, M. M., Fyer, A. J., & Knowles, J. A. (1999) · Psychiatric Genetics · doi:10.1097/00041444-199903000-00001 · Cited by 67 · see citing works
Serotonergic polymorphisms in patients suffering from alcoholism, anxiety disorders and narcolepsy
Fehr, C., Schleicher, A., Szegedi, A., Anghelescu, I., Klawe, C., Hiemke, C., & Dahmen, N. (2001) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(01)00171-3 · Cited by 56 · see citing works
Arias, B., Arranz, M. J., Gastó, C., et al. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001146 · Cited by 53 · see citing works
Yamada, K., Hattori, E., Shimizu, M., Sugaya, A., Shibuya, H., & Yoshikawa, T. (2001) · Journal of Neural Transmission · doi:10.1007/s007020170033 · Cited by 48 · see citing works
Hamilton, S. P., Slager, S. L., HELLEBY, L., Heiman, G. A., Klein, D. F., Hodge, S. E., Weissman, M. M., Fyer, A. J., & Knowles, J. A. (2000) · Molecular Psychiatry · doi:10.1038/sj.mp.4000788 · Cited by 46 · see citing works
Cholecystokinin- and cholecystokinin-B-receptor gene polymorphisms in panic disorder
Hösing, V. G., Schirmacher, A., Kuhlenbäumer, G., Freitag, C. M., Sand, P. G., Schlesiger, C., Jacob, C., Fritze, J., Franke, P. E., Rietschel, M., et al. (2004) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-0579-5_17 · Cited by 44 · see citing works
Bishop, C., & Walker, P. D. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00516-5 · Cited by 42 · see citing works
Dopamine system genes not linked to social phobia
Kennedy, J. L., Neves-Pereira, M., King, N. A., Lizak, M. V., Basile, V. S., Chartier, M., & Stein, M. B. (2001) · Psychiatric Genetics · doi:10.1097/00041444-200112000-00006 · Cited by 37 · see citing works
Deckert, J., Meyer, J., Catalano, M., Bosi, M. F., Sand, P. G., Bella, D. D., Ortega, G., Stöber, G., Franke, P. E., Nöthen, M. M., et al. (2000) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145700002078 · Cited by 36 · see citing works
Association between the CCK‐A receptor gene and panic disorder
Ise, K., Akiyoshi, J., Horinouchi, Y., Tsutsumi, T., Isogawa, K., & Nagayama, H. (2003) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.10020 · Cited by 34 · see citing works
Tachikawa, H., Harada, S., Kawanishi, Y., Okubo, T., & Suzuki, T. (2001) · Psychiatry Research · doi:10.1016/s0165-1781(01)00276-1 · Cited by 34 · see citing works
Hattori, E., Yamada, K., Toyota, T., et al. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.10043 · Cited by 34 · see citing works
Bowen, T., Norton, N., Jacobsen, N., et al. (1998) · Molecular Psychiatry · doi:10.1038/sj.mp.4000293 · Cited by 34 · see citing works
Fehr, C., Szegedi, A., Anghelescu, I., et al. (2000) · Psychiatric Genetics · doi:10.1097/00041444-200010020-00001 · Cited by 32 · see citing works
The genetics of panic disorder
Finn, C. T., & Smoller, J. W. (2001) · Current Psychiatry Reports · doi:10.1007/s11920-001-0010-5 · Cited by 29 · see citing works
Behavioral phenotypes: Conceptual and methodological issues
Flint, J. (1998) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19980508)81:3 · Cited by 28 · see citing works
Oswald, P., Souery, D., Massat, I., et al. (2003) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(03)00041-5 · Cited by 24 · see citing works
Neurobiology of anxiety and fear: challenges for genomic science of the new millennium
Moldin, S. O. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00943-4 · Cited by 20 · see citing works
Ishiguro, H., Saito, T., Shibuya, H., et al. (1999) · Psychiatry Research · doi:10.1016/s0165-1781(98)00127-9 · Cited by 16 · see citing works
Major depression, minor depression, and double depression: are they distinct clinical entities?
Remick, R. A., Sadovnick, A. D., Lam, R. W., Zis, A. P., & Yee, I. M. L. (1996) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19960726)67:4
Donnelly, S. L., Wolpert, C. M., Menold, M. M., Bass, M. P., Gilbert, J. R., Cuccaro, M. L., Delong, G. R., & Pericak-Vance, M. A. (2000) · American Journal of Medical Genetics · doi:10.1002/1096-8628(20000612)96:3
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- Authors
- Maron, E., Nikopensius, T., K??ks, S., Altm??e, S., Heinaste, E., Vabrit, K., Tammekivi, V., Hallast, P., Koido, K., Kurg, A., Metspalu, A., Vasar, E., Vasar, V., & Shlik, J.
- Affiliations
- University of Tartu (EE)
- Estonian Biocentre (EE)
- Asper Biotech (Estonia) (EE)
- University of Ottawa (CA)
- Corresponding author
- Maron, Eduard
- ORCID
- Venue
- Psychiatric Genetics
- Published
- 2005-03
- Volume
- 15
- Issue
- 1
- Pages
- 17-24
- ISSN
- 0955-8829 (ISSN-L)
- OpenAlex
- W1988834331
- Cited by
- 89
- References
- 58
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 4 · 2012: 13
- FWCI
- 12.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Murdoch University Research Portal (submittedVersion)
- Funders
- Chinese Academy of Agricultural Sciences
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- panic disorder, single nucleotide polymorphisms, candidate genes, genetic susceptibility, serotonergic system, cholecystokinin, dopamine, opioid system, HTR2A, dopamine D1 receptor, haplotype analysis
- MeSH terms
- Cholecystokinin, Depressive Disorder, DNA, Genotype, Humans, Polymorphism, Genetic, Receptors, Dopamine, Receptors, Serotonin, Reference Values, Comorbidity, Panic Disorder, DNA Primers, Oligonucleotide Array Sequence Analysis
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