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Characteristics of Japanese inflammatory bowel disease susceptibility loci

  • Original Article—ALIMENTARY TRACT
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Abstract

Background

There are substantial differences in inflammatory bowel disease (IBD) genetics depending on the populations examined. We aimed to identify Japanese population-specific or true culprit susceptibility genes through a meta-analysis of past genetic studies of Japanese IBD.

Methods

For this study, we reviewed 2,703 articles. The review process consisted of three screening stages: we initially searched for relevant studies and then relevant single nucleotide polymorphisms (SNPs). Finally, we adjusted them for the meta-analysis. To maximize our chances of analysis, we introduced proxy SNPs during the first stage. To minimize publication bias, no significant SNPs and solitary SNPs without pairs were combined to be reconsidered during the third stage. Additionally, two SNPs were newly genotyped. Finally, we conducted a meta-analysis of 37 published studies in 50 SNPs located at 22 loci corresponding to the total number of 4,853 Crohn’s disease (CD), 5,612 ulcerative colitis (UC) patients, and 14,239 healthy controls.

Results

We confirmed that the NKX2–3 polymorphism is associated with common susceptibility to IBD and that HLA-DRB1*0450 alleles increase susceptibility to CD but reduce risk for UC while HLA-DRB1*1502 alleles increase susceptibility to UC but reduce CD risk. Moreover, we found individual disease risk loci: TNFSF15 and TNFα to CD and HLA-B*5201, and NFKBIL1 to UC. The genetic risk of HLA was substantially high (odds ratios ranged from 1.54 to 2.69) while that of common susceptibility loci to IBD was modest (odds ratio ranged from 1.13 to 1.24).

Conclusions

Results indicate that Japanese IBD susceptibility loci identified by the meta-analysis are closely associated with the HLA regions.

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References

  1. Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol. 2010;28:573–621.

    Article  CAS  PubMed  Google Scholar 

  2. Hibi T, Ogata H. Novel pathophysiological concepts of inflammatory bowel disease. J Gastroenterol. 2006;41:10–6.

    Article  PubMed  Google Scholar 

  3. Kuwahara E, Asakura K, Nishiwaki Y, Inoue N, Watanabe M, Hibi T, et al. Effect of family history on inflammatory bowel disease characteristics in Japanese patients. J Gastroenterol. 2012;47:961–8.

    Article  CAS  PubMed  Google Scholar 

  4. Van Limbergen J, Russell RK, Nimmo ER, Satsangi J. The genetics of inflammatory bowel disease. Am J Gastroenterol. 2007;102:2820–31.

    Article  PubMed  Google Scholar 

  5. Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, Fisher SA, et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat Genet. 2007;39:830–2.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Silverberg MS, Cho JH, Rioux JD, McGovern DP, Wu J, Annese V, et al. Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. Nat Genet. 2009;41:216–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Franke A, Balschun T, Sina C, Ellinghaus D, Häsler R, Mayr G, et al. Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL). Nat Genet. 2010;42:292–4.

    Article  CAS  PubMed  Google Scholar 

  8. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491:119–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature. 2001;411:599–603.

    Article  CAS  PubMed  Google Scholar 

  10. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. 2007;39:207–11.

    Article  CAS  PubMed  Google Scholar 

  11. Steinman L. A brief history of Th17, the first major revision in the Th1/Th2 hypothesis of T cell-mediated tissue damage. Nat Med. 2007;13:139–45.

    Article  CAS  PubMed  Google Scholar 

  12. Rioux JD, Daly MJ, Silverberg MS, Lindblad K, Steinhart H, Cohen Z, et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet. 2001;29:223–8.

    Article  CAS  PubMed  Google Scholar 

  13. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL-23R as an inflammatory bowel disease gene. Science. 2006;314:1461–3.

    Article  CAS  PubMed  Google Scholar 

  14. Inoue N, Tamura K, Kinouchi Y, Fukuda Y, Takahashi S, Ogura Y, et al. Lack of common NOD2 variants in Japanese patients with Crohn’s disease. Gastroenterology. 2002;123:86–91.

    Article  CAS  PubMed  Google Scholar 

  15. Yamazaki K, Takazoe M, Tanaka T, Ichimori T, Saito S, Iida A, et al. Association analysis of SLC22A4, SLC22A5 and DLG5 in Japanese patients with Crohn disease. J Hum Genet. 2004;49:664–8.

    Article  CAS  PubMed  Google Scholar 

  16. Yamazaki K, Onouchi Y, Takazoe M, Kubo M, Nakamura Y, Hata A. Association analysis of genetic variants in IL23R, ATG16L1 and 5p13.1 loci with Crohn’s disease in Japanese patients. J Hum Genet. 2007;52:575–83.

    Article  CAS  PubMed  Google Scholar 

  17. Yamazaki K, McGovern D, Ragoussis J, Paolucci M, Butler H, Jewell D, et al. Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn’s disease. Hum Mol Genet. 2005;14:3499–506.

    Article  CAS  PubMed  Google Scholar 

  18. Asano K, Matsushita T, Umeno J, Hosono N, Takahashi A, Kawaguchi T, et al. A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. Nat Genet. 2009;41:1325–9.

    Article  CAS  PubMed  Google Scholar 

  19. Okada Y, Yamazaki K, Umeno J, Takahashi A, Kumasaka N, Ashikawa K, et al. HLA-Cw*1202-B*5201-DRB1*1502 haplotype increases risk for ulcerative colitis but reduces risk for Crohn’s disease. Gastroenterology. 2011;141:864–71.

    Article  CAS  PubMed  Google Scholar 

  20. Yamazaki K, Umeno J, Takahashi A, Hirano A, Johnson TA, Kumasaka N, et al. A genome-wide association study identifies 2 susceptibility loci for Crohn’s disease in a Japanese population. Gastroenterology. 2013;144:781–8.

    Article  CAS  PubMed  Google Scholar 

  21. Moher D, Liberati A, Tetzlaff J, Altman DG, the PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–75.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Wang Z, Hu J, Fan R, Zhou J, Zhong J. Association between CD14 gene C-260T polymorphism and inflammatory bowel disease: a meta-analysis. PLoS ONE. 2012;7:e45144.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Seiderer J, Elben I, Diegelmann J, Glas J, Stallhofer J, Tillack C, et al. Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn’s disease and analysis of the IL17F p.His161Arg polymorphism in IBD. Inflamm Bowel Dis. 2008;14:437–45.

    Article  PubMed  Google Scholar 

  25. Tanaka M, Arimura Y, Goto A, Hosokawa M, Nagaishi K, Yamashita K, et al. Genetic variants in surfactant, pulmonary-associated protein D (SFTPD) and Japanese susceptibility to ulcerative colitis. Inflamm Bowel Dis. 2009;15:918–25.

    Article  PubMed  Google Scholar 

  26. Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2–6.

    Article  CAS  PubMed  Google Scholar 

  27. Thakkinstian A, McElduff P, D’Este C, Duffy D, Attia J. A method for meta-analysis of molecular association studies. Stat Med. 2005;24:1291–306.

    Article  PubMed  Google Scholar 

  28. Breslow NE, Day NE. Statistical methods in cancer research. Volume 1—the analysis of case–control studies. Lyon, UK International Agency for Research on Cancer. IARC Sci Publ. 1980;32:5–338.

    PubMed  Google Scholar 

  29. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Weir BS. Genetic data analysis II. Sunderland: Sinauer Associates; 1996.

    Google Scholar 

  31. Arai T, Kakuta Y, Kinouchi Y, Kimura T, Negoro K, Aihara H, et al. Increased expression of NKX2.3 mRNA transcribed from the risk haplotype for ulcerative colitis in the involved colonic mucosa. Hum Immunol. 2011;72:587–91.

    Article  CAS  PubMed  Google Scholar 

  32. Yamazaki K, Takahashi A, Takazoe M, Kubo M, Onouchi Y, Fujino A, et al. Positive association of genetic variants in the upstream region of NKX2-3 with Crohn’s disease in Japanese patients. Gut. 2009;58:228–32.

    Article  CAS  PubMed  Google Scholar 

  33. Nakagome S, Takeyama Y, Mano S, Sakisaka S, Matsui T, Kawamura S, et al. Population-specific susceptibility to Crohn’s disease and ulcerative colitis; dominant and recessive relative risks in the Japanese population. Ann Hum Genet. 2010;74:126–36.

    Article  PubMed  Google Scholar 

  34. Kakuta Y, Kinouchi Y, Negoro K, Takahashi S, Shimosegawa T. Association study of TNFSF15 polymorphisms in Japanese patients with inflammatory bowel disease. Gut. 2006;55:1527–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Prescott NJ, Dominy KM, Kubo M, Lewis CM, Fisher SA, Redon R, et al. Independent and population-specific association of risk variants at the IRGM locus with Crohn’s disease. Hum Mol Genet. 2010;19:1828–39.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Hayashi R, Tahara T, Shiroeda H, Saito T, Nakamura M, Tsutsumi M, et al. Influence of IL17A polymorphisms (rs2275913 and rs3748067) on the susceptibility to ulcerative colitis. Clin Exp Med. 2012;. doi:10.1007/s10238-012-0206-5.

    Google Scholar 

  37. Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al. The influence of polymorphisms of interleukin-17A and interleukin-17F genes on the susceptibility to ulcerative colitis. J Clin Immunol. 2008;28:44–9.

    Article  CAS  PubMed  Google Scholar 

  38. Takagawa T, Tamura K, Takeda N, Tomita T, Ohda Y, Fukunaga K, et al. Association between IL-18 gene promoter polymorphisms and inflammatory bowel disease in a Japanese population. Inflamm Bowel Dis. 2005;11:1038–43.

    Article  CAS  PubMed  Google Scholar 

  39. Tamura K, Fukuda Y, Sashio H, Takeda N, Bamba H, Kosaka T, et al. IL18 polymorphism is associated with an increased risk of Crohn’s disease. J Gastroenterol. 2002;37:111–6.

    Article  CAS  PubMed  Google Scholar 

  40. Sashio H, Tamura K, Ito R, Yamamoto Y, Bamba H, Kosaka T, et al. Polymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and Crohn’s disease, respectively. Immunogenetics. 2002;53:1020–7.

    Article  CAS  PubMed  Google Scholar 

  41. Negoro K, Kinouchi Y, Hiwatashi N, Takahashi S, Takagi S, Satoh J, et al. Crohn’s disease is associated with novel polymorphisms in the 5′-flanking region of the tumor necrosis factor gene. Gastroenterology. 1999;117:1062–8.

    Article  CAS  PubMed  Google Scholar 

  42. Matsuoka M, Sudo S, Nakamura M, Sugisaka H, Negishi M, Miyakawa Y, et al. Genetic association analysis of TNF-α and CD14 gene polymorphism with inflammatory bowel disease. Jpn J Gastroenterol. 2003;100(Suppl):A711 (in Japanese).

    Google Scholar 

  43. Aoyagi Y, Nagata S, Kudo T, Fujii T, Wada M, Chiba Y, et al. Peroxisome proliferator-activated receptor γ 2 mutation may cause a subset of ulcerative colitis. Pediatr Int. 2010;52:729–34.

    Article  CAS  PubMed  Google Scholar 

  44. Wang F, Tahara T, Arisawa T, Sakata M, Takahama K, Watanabe M, et al. Polymorphism of peroxisome proliferator-activated receptor gamma is not associated to Japanese ulcerative colitis. Hepatogastroenterology. 2008;55:73–5.

    CAS  PubMed  Google Scholar 

  45. Sato K, Shiota M, Fukuda S, Iwamoto E, Machida H, Inamine T, et al. Strong evidence of a combination polymorphism of the tyrosine kinase 2 gene and the signal transducer and activator of transcription 3 gene as a DNA-based biomarker for susceptibility to Crohn’s disease in the Japanese population. J Clin Immunol. 2009;29:815–25.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Machida H, Tsukamoto K, Wen CY, Narumi Y, Shikuwa S, Isomoto H, et al. Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese. World J Gastroenterol. 2005;11:4188–93.

    CAS  PubMed  Google Scholar 

  47. Matsuzawa J, Sugimura K, Matsuda Y, Takazoe M, Ishizuka K, Mochizuki T, et al. Association between K469E allele of intercellular adhesion molecule 1 gene and inflammatory bowel disease in a Japanese population. Gut. 2003;52:75–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Narumi Y, Isomoto H, Shiota M, Sato K, Kondo S, Machida H, et al. Polymorphisms of PTPN11 coding SHP-2 as biomarkers for ulcerative colitis susceptibility in the Japanese population. J Clin Immunol. 2009;29:303–10.

    Article  CAS  PubMed  Google Scholar 

  49. Osuga T, Sakaeda T, Nakamura T, Yamada T, Koyama T, Tamura T, et al. MDR1 C3435T polymorphism is predictive of later onset of ulcerative colitis in Japanese. Biol Pharm Bull. 2006;29:324–9.

    Article  CAS  PubMed  Google Scholar 

  50. Kosaka T, Yoshino J, Inui K, Wakabayashi T, Okushima K, Kobayashi T, et al. Association between SHMT gene polymorphisms and ulcerative colitis. Jpn J Gastroenterol. 2009;106(Suppl):A826 (in Japanese).

    Google Scholar 

  51. Shiroeda H, Tahara T, Nakamura M, Shibata T, Nomura T, Yamada H, et al. Association between functional promoter polymorphisms of macrophage migration inhibitory factor (MIF) gene and ulcerative colitis in Japan. Cytokine. 2010;51:173–7.

    Article  CAS  PubMed  Google Scholar 

  52. Nohara H, Okayama N, Inoue N, Koike Y, Fujimura K, Suehiro Y, et al. Association of the −173 G/C polymorphism of the macrophage migration inhibitory factor gene with ulcerative colitis. J Gastroenterol. 2004;39:242–6.

    Article  CAS  PubMed  Google Scholar 

  53. Fuse K, Katakura K, Sakamoto N, Ohira H. Toll-like receptor 9 gene mutations and polymorphisms in Japanese ulcerative colitis patients. World J Gastroenterol. 2010;16:5815–21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Wang F, Tahara T, Arisawa T, Shibata T, Nakamura M, Fujita H, et al. Genetic polymorphisms of CD14 and Toll-like receptor-2 (TLR2) in patients with ulcerative colitis. J Gastroenterol Hepatol. 2007;22:925–9.

    Article  CAS  PubMed  Google Scholar 

  55. Obana N, Takahashi S, Kinouchi Y, Negoro K, Takagi S, Hiwatashi N, et al. Ulcerative colitis is associated with a promoter polymorphism of lipopolysaccharide receptor gene, CD14. Scand J Gastroenterol. 2002;37:699–704.

    Article  CAS  PubMed  Google Scholar 

  56. Oomori S. Association between polymorphisms in the inhibitor of Kappa B-like protein (IKBL) gene and ulcerative colitis in a Japanese population. Med J Sendai Red Cross Hosp. 2009;18:23–32 (in Japanese).

    Google Scholar 

  57. Aizawa H, Kinouchi Y, Negoro K, Nomura E, Imai G, Takahashi S, et al. HLA-B is the best candidate of susceptibility genes in HLA for Japanese ulcerative colitis. Tissue Antigens. 2009;73:569–74.

    Article  CAS  PubMed  Google Scholar 

  58. Kinouchi Y, Matsumoto K, Negoro K, Takagi S, Takahashi S, Hiwatashi N, et al. HLA-B genotype in Japanese patients with Crohn’s disease. Dis Colon Rectum. 2003;46:S10–4.

    PubMed  Google Scholar 

  59. Seki SS, Sugimura K, Ota M, Matsuzawa J, Katsuyama Y, Ishizuka K, et al. Stratification analysis of MICA triplet repeat polymorphisms and HLA antigens associated with ulcerative colitis in Japanese. Tissue Antigens. 2001;58:71–6.

    Article  CAS  PubMed  Google Scholar 

  60. Futami S, Aoyama N, Honsako Y, Tamura T, Morimoto S, Nakashima T, et al. HLA-DRB1*1502 allele, subtype of DR15, is associated with susceptibility to ulcerative colitis and its progression. Dig Dis Sci. 1995;40:814–8.

    Article  CAS  PubMed  Google Scholar 

  61. Matsumura Y, Kinouchi Y, Nomura E, Negoro K, Kakuta Y, Endo K, et al. HLA-DRB1 alleles influence clinical phenotypes in Japanese patients with ulcerative colitis. Tissue Antigens. 2008;71:447–52.

    Article  CAS  PubMed  Google Scholar 

  62. Tremelling M, Berzuini C, Massey D, Bredin F, Price C, Dawson C, et al. Contribution of TNFSF15 gene variants to Crohn’s disease susceptibility confirmed in UK population. Inflamm Bowel Dis. 2008;14:733–7.

    Article  PubMed  Google Scholar 

  63. Takedatsu H, Michelsen KS, Wei B, Landers CJ, Thomas LS, Dhall D, et al. TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. Gastroenterology. 2008;135:552–67.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Lawrence PA, Morata G. Homeobox genes: their function in Drosophila segmentation and pattern formation. Cell. 1994;78:181–9.

    Article  CAS  PubMed  Google Scholar 

  65. Buchberger A, Pabst O, Brand T, Seidl K, Arnold HH. Chick NKx-2.3 represents a novel family member of vertebrate homologues to the Drosophila homeobox gene tinman: differential expression of cNKx-2.3 and cNKx-2.5 during heart and gut development. Mech Dev. 1996;56:151–63.

    Article  CAS  PubMed  Google Scholar 

  66. Fu Y, Yan W, Mohun TJ, Evans SM. Vertebrate tinman homologues XNk2–3 and XNk2–5 are required for heart formation in a functionally redundant manner. Development. 1998;125:4439–49.

    CAS  PubMed  Google Scholar 

  67. Wang CC, Biben C, Robb L, Nassir F, Barnett L, Davidson NO, et al. Homeodomain factor Nk2–3 controls regional expression of leukocyte homing coreceptor MAdCAM-1 in specialized endothelial cells of the viscera. Dev Biol. 2000;224:152–67.

    Article  CAS  PubMed  Google Scholar 

  68. Pabst O, Förster R, Lipp M, Engel H, Arnold HH. NKX2.3 is required for MAdCAM-1 expression and homing of lymphocytes in spleen and mucosa-associated lymphoid tissue. EMBO J. 2000;19:2015–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Stokkers PC, Reitsma PH, Tytgat GN, van Deventer SJ. HLA-DR and -DQ phenotypes in inflammatory bowel disease: a meta-analysis. Gut. 1999;45:395–401.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Ahmad T, Marshall SE, Jewell D. Genetics of inflammatory bowel disease: the role of the HLA complex. World J Gastroenterol. 2006;12:3628–35.

    CAS  PubMed  Google Scholar 

  71. Yang SK, Hong M, Zhao W, Jung Y, Baek J, Tayebi N, et al. Genome-wide association study of Crohn’s disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations. Gut. 2013;. doi:10.1136/gutjnl-2013-305193.

    Google Scholar 

  72. Ng SC, Tsoi KK, Kamm MA, Xia B, Wu J, Chan FK, et al. Genetics of inflammatory bowel disease in Asia: systematic review and meta-analysis. Inflamm Bowel Dis. 2012;6:1164–76.

    Article  Google Scholar 

  73. Franke A, Balschun T, Karlsen TH, Hedderich J, May S, Lu T, et al. Replication of signals from recent studies of Crohn’s disease identifies previously unknown disease loci for ulcerative colitis. Nat Genet. 2008;40:713–5.

    Article  CAS  PubMed  Google Scholar 

  74. International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). Ulcerative colitis meta-analysis summary statistics. http://www.ibdgenetics.org/downloads.html.

  75. Fernando MM, Stevens CR, Walsh EC, De Jager PL, Goyette P, Plenge RM, et al. Defining the role of the MHC in autoimmunity: a review and pooled analysis. PLoS Genet. 2008;4:e1000024.

    Article  PubMed Central  PubMed  Google Scholar 

  76. Ahmad T, Armuzzi A, Neville M, Bunce M, Ling KL, et al. The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis. Tissue Antigens. 2003;62:527–35.

    Article  CAS  PubMed  Google Scholar 

  77. Roussomoustakaki M, Satsangi J, Welsh K, Louis E, Fanning G, et al. Genetic markers may predict disease behavior in patients with ulcerative colitis. Gastroenterology. 1997;112:1845–53.

    Article  CAS  PubMed  Google Scholar 

  78. Ahmad T, Marshall SE, Jewell D. Genetics of inflammatory bowel disease: the role of the HLA complex. World J Gastroenterol. 2006;12:3628–35.

    CAS  PubMed  Google Scholar 

  79. Chervonsky AV. Influence of microbial environment on autoimmunity. Nat Immunol. 2010;11:28–35.

    Article  CAS  PubMed  Google Scholar 

  80. Birney E. Chromatin and heritability: how epigenetic studies can complement genetic approaches. Trends Genet. 2011;5:172–6.

    Article  Google Scholar 

  81. Liu Y, Aryee MJ, Padyukov L, Fallin MD, Hesselberg E, Runarsson A, et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat Biotechnol. 2013;2:142–7.

    Article  Google Scholar 

  82. Ventham NT, Kennedy NA, Nimmo ER, Satsangi J. Beyond gene discovery in inflammatory bowel disease: the emerging role of epigenetics. Gastroenterology. 2013;145:293–308.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by Health and Labor Sciences Research Grants for Research on Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan (Y.A.). We are very grateful to Dr. Y Numata, Dr. H Nasuno, and Dr. Y Ishimine, residents of the First Department of Internal Medicine, for their resource collection.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, Rheumatology, and Clinical Immunology, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan

    Yoshiaki Arimura, Hiroyuki Isshiki, Kei Onodera, Kentaro Yamashita & Yasuhisa Shinomura

  2. Department of Anatomy, Sapporo Medical University, Sapporo, Japan

    Kanna Nagaishi & Mineko Fujimiya

  3. Department of Public Health, Sapporo Medical University, Sapporo, Japan

    Tomoko Sonoda

  4. Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Takayuki Matsumoto

  5. Laboratory for Statistical Analysis, Center for Integrative Medical Science, RIKEN, Tokyo, Japan

    Atsushi Takahashi

  6. Division of Gastroenterology, Department of Medicine, Social Insurance Chuo General Hospital, Tokyo, Japan

    Masakazu Takazoe

  7. Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan

    Keiko Yamazaki & Michiaki Kubo

  8. Center for Antibody and Vaccine Therapy, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    Kohzoh Imai

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  1. Yoshiaki Arimura
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Arimura, Y., Isshiki, H., Onodera, K. et al. Characteristics of Japanese inflammatory bowel disease susceptibility loci. J Gastroenterol 49, 1217–1230 (2014). https://doi.org/10.1007/s00535-013-0866-2

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