Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
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Association Study of ANK3 Polymorphism and Risk of Schizophrenia

ANK3 유전자 다형성과 조현병의 연관성에 대한 연합연구

  • Yang, So Yung (Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center) ;
  • Huh, Ik-Soo (Department of Statistics, Seoul National University) ;
  • Cho, Eun Young (Center for Clinical Research, Samsung Biomedical Research Institute) ;
  • Choi, Mi Ji (Center for Clinical Research, Samsung Biomedical Research Institute) ;
  • Park, Taesung (Department of Statistics, Seoul National University) ;
  • Lee, Yu-Sang (Yong-In Mental Hospital) ;
  • Hong, Kyung Sue (Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center)
  • 양소영 (성균관대학교 의과대학 삼성서울병원 정신건강의학교실) ;
  • 허익수 (서울대학교 자연과학대학 통계학과) ;
  • 조은영 (삼성생명과학연구소 임상의학연구센터) ;
  • 최미지 (삼성생명과학연구소 임상의학연구센터) ;
  • 박태성 (서울대학교 자연과학대학 통계학과) ;
  • 이유상 (용인정신병원) ;
  • 홍경수 (성균관대학교 의과대학 삼성서울병원 정신건강의학교실)
  • Received : 2015.07.13
  • Accepted : 2015.08.26
  • Published : 2015.11.30
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Abstract

Objectives Previous genome-wide association studies have indicated the association between ankyrin 3 (ANK3) and the vulnerability of schizophrenia. We investigated the association between single nucleotide polymorphisms (SNPs) covering the whole ANK3 locus and schizophrenia in the Korean population. Methods The study subjects were 582 patients with schizophrenia and 502 healthy controls. Thirty-eight tag SNPs on ANK3 and five additional SNPs showing significant association with schizophrenia in previous studies were genotyped. Results Three (rs10994181, rs16914791, rs1938526) of 43 SNPs showed a nominally significant association (p < 0.05) with at least one genotype model. But none of these associations remained significant after adjusting for multiple testing errors with Bonferroni's correction. Conclusions We could not identify a significant association between ANK3 and schizophrenia in the Korean population. However, three SNPs showing an association signal with nominal significance need to be investigated in future studies with higher statistical power and more specific phenotype crossing the current diagnostic categories.

Keywords

References

  1. McGuffin P, Asherson P, Owen M, Farmer A. The strength of the genetic effect. Is there room for an environmental influence in the aetiology of schizophrenia? Br J Psychiatry 1994;164:593-599. https://doi.org/10.1192/bjp.164.5.593
  2. McGuffin P, Farmer AE, Gottesman II, Murray RM, Reveley AM. Twin concordance for operationally defined schizophrenia. Confirmation of familiality and heritability. Arch Gen Psychiatry 1984;41:541-545. https://doi.org/10.1001/archpsyc.1984.01790170015002
  3. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature 2014;511:421-427. https://doi.org/10.1038/nature13595
  4. Baum AE, Akula N, Cabanero M, Cardona I, Corona W, Klemens B, et al. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry 2008;13:197-207. https://doi.org/10.1038/sj.mp.4002012
  5. Ferreira MA, O'Donovan MC, Meng YA, Jones IR, Ruderfer DM, Jones L, et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 2008;40:1056-1058. https://doi.org/10.1038/ng.209
  6. Schulze TG, Detera-Wadleigh SD, Akula N, Gupta A, Kassem L, Steele J, et al. Two variants in Ankyrin 3 (ANK3) are independent genetic risk factors for bipolar disorder. Mol Psychiatry 2009;14:487-491. https://doi.org/10.1038/mp.2008.134
  7. Takata A, Kim SH, Ozaki N, Iwata N, Kunugi H, Inada T, et al. Association of ANK3 with bipolar disorder confirmed in East Asia. Am J Med Genet B Neuropsychiatr Genet 2011;156B:312-315.
  8. Chen DT, Jiang X, Akula N, Shugart YY, Wendland JR, Steele CJ, et al. Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder. Mol Psychiatry 2013;18:195-205. https://doi.org/10.1038/mp.2011.157
  9. Athanasiu L, Mattingsdal M, Kahler AK, Brown A, Gustafsson O, Agartz I, et al. Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort. J Psychiatr Res 2010;44:748-753. https://doi.org/10.1016/j.jpsychires.2010.02.002
  10. Yuan A, Yi Z, Wang Q, Sun J, Li Z, Du Y, et al. ANK3 as a risk gene for schizophrenia: new data in Han Chinese and meta analysis. Am J Med Genet B Neuropsychiatr Genet 2012;159B:997-1005. https://doi.org/10.1002/ajmg.b.32112
  11. Moskvina V, Craddock N, Holmans P, Nikolov I, Pahwa JS, Green E, et al. Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for overlap in genetic risk. Mol Psychiatry 2009;14:252-260. https://doi.org/10.1038/mp.2008.133
  12. International Schizophrenia Consortium, Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009;460:748-752.
  13. Gella A, Segura M, Durany N, Pfuhlmann B, Stober G, Gawlik M. Is Ankyrin a genetic risk factor for psychiatric phenotypes? BMC Psychiatry 2011;11:103. https://doi.org/10.1186/1471-244X-11-103
  14. Kordeli E, Lambert S, Bennett V. AnkyrinG. A new ankyrin gene with neural-specific isoforms localized at the axonal initial segment and node of Ranvier. J Biol Chem 1995;270:2352-2359. https://doi.org/10.1074/jbc.270.5.2352
  15. Pan Z, Kao T, Horvath Z, Lemos J, Sul JY, Cranstoun SD, et al. A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon. J Neurosci 2006;26:2599-2613. https://doi.org/10.1523/JNEUROSCI.4314-05.2006
  16. Zhou D, Lambert S, Malen PL, Carpenter S, Boland LM, Bennett V. AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing. J Cell Biol 1998;143:1295-1304. https://doi.org/10.1083/jcb.143.5.1295
  17. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005;21:263-265. https://doi.org/10.1093/bioinformatics/bth457
  18. de Bakker PI, Yelensky R, Pe'er I, Gabriel SB, Daly MJ, Altshuler D. Efficiency and power in genetic association studies. Nat Genet 2005;37:1217-1223. https://doi.org/10.1038/ng1669
  19. Clayton D. snpStats: SnpMatrix and XSnpMatrix classes and methods. R package version 1.18.0;2014.
  20. Lee MT, Chen CH, Lee CS, Chen CC, Chong MY, Ouyang WC, et al. Genome-wide association study of bipolar I disorder in the Han Chinese population. Mol Psychiatry 2011;16:548-556. https://doi.org/10.1038/mp.2010.43
  21. Roussos P, Katsel P, Davis KL, Bitsios P, Giakoumaki SG, Jogia J, et al. Molecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia. Arch Gen Psychiatry 2012;69:7-15. https://doi.org/10.1001/archgenpsychiatry.2011.110
  22. Wirgenes KV, Tesli M, Inderhaug E, Athanasiu L, Agartz I, Melle I, et al. ANK3 gene expression in bipolar disorder and schizophrenia. Br J Psychiatry 2014;205:244-245. https://doi.org/10.1192/bjp.bp.114.145433
  23. Zhang C, Cai J, Zhang J, Li Z, Guo Z, Zhang X, et al. Genetic modulation of working memory deficits by ankyrin 3 gene in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2014;50:110-115. https://doi.org/10.1016/j.pnpbp.2013.12.010
  24. Tandon R, Keshavan MS, Nasrallah HA. Schizophrenia, "just the facts" what we know in 2008. 2. Epidemiology and etiology. Schizophr Res 2008;102:1-18.
  25. Braff DL, Freedman R, Schork NJ, Gottesman II. Deconstructing schizophrenia: an overview of the use of endophenotypes in order to understand a complex disorder. Schizophr Bull 2007;33:21-32.
  26. Keshavan MS, Morris DW, Sweeney JA, Pearlson G, Thaker G, Seidman LJ, et al. A dimensional approach to the psychosis spectrum between bipolar disorder and schizophrenia: the Schizo-Bipolar Scale. Schizophr Res 2011;133:250-254. https://doi.org/10.1016/j.schres.2011.09.005