Abstract
Panic disorder (PD) is an anxiety disorder characterized by panic attacks and anticipatory anxiety. Although a number of association studies have been conducted, no gene has been identified as a susceptibility locus. In this study, we conducted a genome-wide association study of PD in 200 Japanese patients and the same number of controls, using the GeneChip Human Mapping 500 K Array Set. Genotypes were determined using the Bayesian Robust Linear Model with Mahalanobis (BRLMM) genotype calling algorithm. The genotype data were data-cleaned using criteria for SNP call rate (⩾95%), Hardy–Weinberg equilibrium (P⩾0.1%) and minor allele frequency (⩾5%). The significance level of the allele P-value was set at 1.0 × 10−6, to make false discovery rate (FDR) <0.05. As a result, seven SNPs were significantly associated with PD, which were located in or adjacent to genes including PKP1, PLEKHG1, TMEM16B, CALCOCO1, SDK2 and CLU (or APO-J). Studies with other samples are required to confirm the results.
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References
Eaton, W. W., Kessler, R. C., Wittchen, H. U. & Magee, W. J. Panic and panic disorder in the United States. Am. J. Psychiatry 151, 413–420 (1994).
Inada, Y., Yoneda, H., Koh, J., Sakai, J., Himei, A ., Kinoshita, Y. et al. Positive association between panic disorder and polymorphism of the serotonin 2A receptor gene. Psychiatry Res. 118, 25–31 (2003).
Rothe, C., Gutknecht, L., Freitag, C., Tauber, R., Mossner, R ., Franke, P. et al. Association of a functional 1019C>G 5-HT1A receptor gene polymorphism with panic disorder with agoraphobia. Int. J. Neuropsychopharmacol. 7, 189–192 (2004).
Rothe, C., Koszycki, D., Bradwejn, J., King, N., De Luca, V ., Shaikh, S et al. Association study of serotonin-2A receptor gene polymorphism and panic disorder in patients from Canada and Germany. Neurosci. Lett. 363, 276–279 (2004).
Hattori, E., Yamada, K., Toyota, T., Yoshitsugu, K., Toru, M ., Shibuya, H et al. Association studies of the CT repeat polymorphism in the 5′ upstream region of the cholecystokinin B receptor gene with panic disorder and schizophrenia in Japanese subjects. Am. J. Med. Genet. 105, 779–782 (2001).
Ebihara, M., Ohba, H., Hattori, E., Yamada, K. & Yoshikawa, T. Transcriptional activities of cholecystokinin promoter haplotypes and their relevance to panic disorder susceptibility. Am. J. Med. Genet 118, 32–35 (2003).
Deckert, J., Nothen, M. M., Franke, P., Delmo, C., Fritze, J ., Knapp, M. et al. Systematic mutation screening and association study of the A1 and A2a adenosine receptor genes in panic disorder suggest a contribution of the A2a gene to the development of disease. Mol. Psychiatry 3, 81–85 (1998).
Hamilton, S. P., Slager, S. L., Heiman, G. A., Deng, Z., Haghighi, F ., Klein, D. F et al. Evidence for a susceptibility locus for panic disorder near the catechol-O-methyltransferase gene on chromosome 22. Biol. Psychiatry 51, 591–601 (2002).
Woo, J. M., Yoon, K. S. & Yu, B. H. Catechol O-methyltransferase genetic polymorphism in panic disorder. Am. J. Psychiatry 159, 1785–1787 (2002).
Woo, J. M., Yoon, K. S., Choi, Y. H., Oh, K. S., Lee, Y. S. & Yu, B. H. The association between panic disorder and the L/L genotype of catechol-O-methyltransferase. J. Psychiatr. Res. 38, 365–370 (2004).
Deckert, J., Catalano, M., Syagailo, Y. V., Bosi, M., Okladnova, O ., Di Bella, D. et al. Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Hum. Mol. Genet. 8, 621–624 (1999).
Wellcome Trust Case Control Consortium. Genome-wide association study of 14 000 cases of seven common diseases and 3000 shared controls. Nature 447, 661–678 (2007).
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th edn (American Psychiatric Association, Washington D.C., 1994).
Rabbee, N. & Speed, T. P. A genotype calling algorithm for affymetrix SNP arrays. Bioinformatics 22, 7–12 (2006).
Miyagawa, T., Nishida, N., Ohashi, J., Kimura, R., Fujimoto, A ., Kawashima, M. et al. Appropriate data cleaning methods for genome-wide association study. J. Hum. Genet. 53, 886–893 (2008).
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B. 57, 289–300 (1995).
Ohashi, J., Yamamoto, S., Tsuchiya, N., Hatta, Y., Komata, T ., Matsushita, M. et al. Comparison of statistical power between 2 * 2 allele frequency and allele positivity tables in case-control studies of complex disease genes. Ann. Hum. Genet. 65, 197–206 (2001).
Ohashi, J. & Tokunaga, K. The expected power of genome-wide linkage disequilibrium testing using single nucleotide polymorphism markers for detecting a low-frequency disease variant. Ann. Hum. Genet. 66, 297–306 (2002).
Hamilton, S. P., Fyer, A. J., Durner, M., Heiman, G. A., Baisre de Leon, A ., Hodge, S. E. et al. Further genetic evidence for a panic disorder syndrome mapping to chromosome 13q. Proc. Natl Acad. Sci. USA 100, 2550–2555 (2003).
Balding, D. J. A tutorial on statistical methods for population association studies. Nat. Rev. Genet. 7, 781–791 (2006).
Acknowledgements
This study was supported by a Grant-in-Aid for Scientific Research on Priority Areas ‘Comprehensive Genomics’ and ‘Applied Genomics’ (no. 17019029) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank Ms Yoshimi Ishibashi and Ms Yuko Ogasawara for technical assistance.
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Otowa, T., Yoshida, E., Sugaya, N. et al. Genome-wide association study of panic disorder in the Japanese population. J Hum Genet 54, 122–126 (2009). https://doi.org/10.1038/jhg.2008.17
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DOI: https://doi.org/10.1038/jhg.2008.17
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