Genetics of autoimmune diseases: Perspectives from genome-wide association studies

International Immunology

Volumn 28, Issue 4, 2016, Pages 155-161

  Kochi, Yuta ^a  

^a Institute of Physical and Chemical Research   (Japan)

Author keywords

Autoimmune disease; Expression quantitative trait locus; Genome wide association study

Indexed keywords

ANTIGEN; BREAKPOINT CLUSTER REGION PROTEIN; INTERFERON; LYMPHOCYTE ANTIGEN RECEPTOR; TOLL LIKE RECEPTOR; HISTOCOMPATIBILITY ANTIGEN;

ANTIGEN PRESENTATION; AUTOIMMUNE DISEASE; GENE EXPRESSION; GENETIC IDENTIFICATION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; HUMAN; IMMUNOCOMPETENT CELL; MAJOR HISTOCOMPATIBILITY COMPLEX; NONHUMAN; PRIORITY JOURNAL; QUANTITATIVE TRAIT LOCUS; REGULATORY T LYMPHOCYTE; REVIEW; SIGNAL TRANSDUCTION; TH1 CELL; TH17 CELL; ANIMAL; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION; IMMUNOLOGY; METABOLISM; T LYMPHOCYTE SUBPOPULATION;

ANIMALS; ANTIGEN PRESENTATION; AUTOIMMUNE DISEASES; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HISTOCOMPATIBILITY ANTIGENS; HUMANS; INTERFERON TYPE I; QUANTITATIVE TRAIT LOCI; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; T-LYMPHOCYTE SUBSETS;

EID: 84964644414     PISSN: 09538178     EISSN: 14602377     Source Type: Journal    
DOI: 10.1093/intimm/dxw002     Document Type: Review

References (80)

1. Lleo, A., Invernizzi, P., Gao, B., Podda, M. and Gershwin, M. E. 2010. Definition of human autoimmunity--autoantibodies versus autoimmune disease. Autoimmun. Rev. 9:A259.
2. Hayter, S. M. and Cook, M. C. 2012. Updated assessment of the prevalence, spectrum and case definition of autoimmune disease. Autoimmun. Rev. 11:754.
3. Okada, Y., Wu, D., Trynka, G. et al. 2014. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506:376.
4. International Multiple Sclerosis Genetics Consortium; Beecham, A. H., Patsopoulos, N. A., Xifara, D. K. et al. 2013. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat. Genet. 45:1353.
5. Jostins, L., Ripke, S.Weersma, R. K. et al. 2012. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119.
6. Gusev, A., Lee, S. H., Trynka, G. et al. 2014. Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases. Am. J. Hum. Genet. 95:535.
7. Dubois, P. C., Trynka, G., Franke, L. et al. 2010. Multiple common variants for celiac disease influencing immune gene expression. Nat. Genet. 42:295.
8. Okada, Y., Shimane, K., Kochi, Y. et al. 2012. A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese. PLoS Genet. 8:e1002455.
9. Raj, T., Rothamel, K., Mostafavi, S. et al. 2014. Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes. Science 344:519.
10. De Jager, P. L., Hacohen, N., Mathis, D. et al. 2015. ImmVar project: Insights and design considerations for future studies of "healthy" immune variation. Semin. Immunol. 27:51.
11. GTEx Consortium; Ardlie, K. G., Deluca, D. S., Segrè, A. V. et al. 2015. Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348:648.
12. ENCODE Project Consortium; Dunham, I., Kundaje, A., Aldred, S. F. et al. 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489:57.
13. Kundaje, A., Meuleman, W., Ernst, J. et al.; Roadmap Epigenomics Consortium. 2015. Integrative analysis of 111 reference human epigenomes. Nature 518:317.
14. Farh, K. K., Marson, A., Zhu, J. et al. 2014. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 518:337.
15. Witte, S., O'Shea, J. J. and Vahedi, G. 2015. Super-enhancers: asset management in immune cell genomes. Trends Immunol. 36:519.
16. Hnisz, D., Abraham, B. J., Lee, T. I. et al. 2013. Super-enhancers in the control of cell identity and disease. Cell 155:934.
17. The Wellcome Trust Case Control Consortium. 2007. Genomewide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661.
18. Breban, M., Costantino, F., Andre, C., Chiocchia, G. and Garchon, H. J. 2015. Revisiting MHC genes in spondyloarthritis. Curr. Rheumatol. Rep. 17:516.
19. Newton, J. L., Harney, S. M., Wordsworth, B. P. and Brown, M. A. 2012. A review of the MHC genetics of rheumatoid arthritis. Genes Immun. 5:151.
20. Gregersen, P. K., Silver, J. and Winchester, R. J. 1987. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 30:1205.
21. Raychaudhuri, S., Sandor, C., Stahl, E. A. et al. 2012. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat. Genet. 44:291.
22. Han, B., Diogo, D., Eyre, S. et al. 2014. Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity. Am. J. Hum. Genet. 94:522.
23. Nejentsev, S., Howson, J. M., Walker, N. M. et al. 2007. Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A. Nature 450:887.
24. Hu, X., Deutsch, A. J., Lenz, T. L. et al. 2015. Additive and interaction effects at three amino acid positions in HLA-DQ and HLA-DR molecules drive type 1 diabetes risk. Nat. Genet. 47:898.
25. Moutsianas, L., Jostins, L., Beecham, A. H. et al.; International Multiple Sclerosis Genetics Consortium. 2015. Class II HLA interactions modulate genetic risk for multiple sclerosis. Nat. Genet. 47:1107.
26. Okada, Y., Momozawa, Y., Ashikawa, K. et al. 2015. Construction of a population-specific HLA imputation reference panel and its application to Graves' disease risk in Japanese. Nat. Genet. 47:798.
27. Sakaguchi, N., Takahashi, T., Hata, H. et al. 2003. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature 426:454.
28. Kumar, K. R., Li, L., Yan, M. et al. 2006. Regulation of B cell tolerance by the lupus susceptibility gene Ly108. Science 312:1665.
29. Gregersen, P. K., Lee, H. S., Batliwalla, F. and Begovich, A. B. 2006. PTPN22: setting thresholds for autoimmunity. Semin. Immunol. 18:214.
30. Arechiga, A. F., Habib, T., He, Y. et al. 2009. Cutting edge: the PTPN22 allelic variant associated with autoimmunity impairs B cell signaling. J. Immunol. 182:3343.
31. Vang, T., Congia, M., Macis, M. D. et al. 2005. Autoimmuneassociated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat. Genet. 37:1317.
32. Begovich, A. B., Carlton, V. E., Honigberg, L. A. et al. 2004. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am. J. Hum. Genet. 75:330.
33. Zhang, J., Zahir, N., Jiang, Q. et al. 2011. The autoimmune disease- associated PTPN22 variant promotes calpain-mediated Lyp/Pep degradation associated with lymphocyte and dendritic cell hyperresponsiveness. Nat. Genet. 43:902.
34. Dai, X., James, R. G., Habib, T. et al. 2013. A disease-associated PTPN22 variant promotes systemic autoimmunity in murine models. J. Clin. Invest. 123:2024.
35. Rawlings, D. J., Dai, X. and Buckner, J. H. 2015. The role of PTPN22 risk variant in the development of autoimmunity: finding common ground between mouse and human. J. Immunol. 194:2977.
36. Stanford, S. M. and Bottini, N. 2014. PTPN22: the archetypal non- HLA autoimmunity gene. Nat. Rev. Rheumatol. 10:602.
37. Manjarrez-Orduño, N., Marasco, E., Chung, S. A. et al. 2012. CSK regulatory polymorphism is associated with systemic lupus erythematosus and influences B-cell signaling and activation. Nat. Genet. 44:1227.
38. Simpfendorfer, K. R., Armstead, B. E., Shih, A. et al. 2015. Autoimmune disease-associated haplotypes of BLK exhibit lowered thresholds for B cell activation and expansion of Ig classswitched B cells. Arthritis Rheumatol. 67:2866.
39. Hom, G., Graham, R. R., Modrek, B. et al. 2008. Association of systemic lupus erythematosus with C8orf13-BLK and ITGAMITGAX. N. Engl. J. Med. 358:900.
40. Dymecki, S. M., Niederhuber, J. E. and Desiderio, S. V. 1990. Specific expression of a tyrosine kinase gene, blk, in B lymphoid cells. Science 247:332.
41. Vahedi, G., Kanno, Y., Furumoto, Y. et al. 2015. Super-enhancers delineate disease-associated regulatory nodes in T cells. Nature 520:558.
42. Duerr, R. H., Taylor, K. D., Brant, S. R. et al. 2006. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461.
43. Nair, R. P., Duffin, K. C., Helms, C. et al. 2009. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat. Genet. 41:199.
44. Reveille, J. D., Sims, A. M., Danoy, P. et al. 2010. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat. Genet. 42:123.
45. Sarin, R., Wu, X. and Abraham, C. 2011. Inflammatory disease protective R381Q IL23 receptor polymorphism results in decreased primary CD4+ and CD8+ human T-cell functional responses. Proc. Natl Acad. Sci. USA 108:9560.
46. Remmers, E. F., Cosan, F., Kirino, Y. et al. 2010. Genome-wide association study identifies variants in the MHC class I, IL10, andIL23R-IL12RB2 regions associated with Behçet's disease. Nat. Genet. 42:698.
47. Mizuki, N., Meguro, A., Ota, M. et al. 2010. Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet's disease susceptibility loci. Nat. Genet. 42:703.
48. Parkes, M., Cortes, A., van Heel, D. A. and Brown, M. A. 2013. Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat. Rev. Genet. 14:661.
49. Hirschfield, G. M., Liu, X., Xu, C. et al. 2009. Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. N. Engl. J. Med. 360:2544.
50. Bossini-Castillo, L., Martin, J. E., Broen, J. et al. 2012. A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations. Hum. Mol. Genet. 21:926.
51. Mayes, M. D., Bossini-Castillo, L., Gorlova, O. et al. 2014. Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis. Am. J. Hum. Genet. 94:47.
52. Jakkula, E., Leppä, V., Sulonen, A. M. et al. 2010. Genome-wide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene. Am. J. Hum. Genet. 86:285.
53. Barrett, J. C., Hansoul, S., Nicolae, D. L. et al. 2008. Genomewide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat. Genet. 40:955.
54. Tsoi, L. C., Spain, S. L., Knight, J. et al. 2012. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat. Genet. 44:1341.
55. Westra, H. J., Peters, M. J., Esko, T. et al. 2013. Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat. Genet. 45:1238.
56. Remmers, E. F., Plenge, R. M., Lee, A. T. et al. 2007. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N. Engl. J. Med. 357:977.
57. Radstake, T. R., Gorlova, O., Rueda, B. et al. 2010. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat. Genet. 42:426.
58. Lessard, C. J., Li, H., Adrianto, I. et al. 2013. Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome. Nat. Genet. 45:1284.
59. Sigurdsson, S., Nordmark, G., Garnier, S. et al. 2008. A risk haplotype of STAT4 for systemic lupus erythematosus is overexpressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF5. Hum. Mol. Genet. 17:2868.
60. Sakaguchi, S., Yamaguchi, T., Nomura, T. and Ono, M. 2008. Regulatory T cells and immune tolerance. Cell 133:775.
61. Trynka, G., Sandor, C., Han, B. et al. 2013. Chromatin marks identify critical cell types for fine mapping complex trait variants. Nat. Genet. 45:124.
62. Kochi, Y., Okada, Y., Suzuki, A. et al. 2010. A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nat. Genet. 42:515.
63. Ferraro, A., D'Alise, A. M., Raj, T. et al. 2014. Interindividual variation in human T regulatory cells. Proc. Natl Acad. Sci. USA 111:E1111.
64. Kochi, Y., Yamada, R., Suzuki, A. et al. 2005. A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities. Nat. Genet. 37:478.
65. Kochi, Y., Myouzen, K., Yamada, R. et al. 2009. FCRL3, an autoimmune susceptibility gene, has inhibitory potential on B-cell receptor- mediated signaling. J. Immunol. 183:5502.
66. Swainson, L. A., Mold, J. E., Bajpai, U. D. and McCune, J. M. 2010. Expression of the autoimmune susceptibility gene FcRL3 on human regulatory T cells is associated with dysfunction and high levels of programmed cell death-1. J. Immunol. 184:3639.
67. Myouzen, K., Kochi, Y., Okada, Y. et al. 2012. Functional variants in NFKBIE and RTKN2 involved in activation of the NF-?B pathway are associated with rheumatoid arthritis in Japanese. PLoS Genet. 8:e1002949.
68. Schmidl, C., Hansmann, L., Lassmann, T. et al. 2014. The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations. Blood 123:e68.
69. Okamura, T., Sumitomo, S., Morita, K. et al. 2015. TGF-beta3- expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses. Nat. Commun. 6:6329.
70. Okamura, T., Fujio, K., Shibuya, M. et al. 2009. CD4+CD25- LAG3+ regulatory T cells controlled by the transcription factor Egr-2. Proc. Natl Acad. Sci. USA 106:13974.
71. Yang, L., Anderson, D. E., Baecher-Allan, C. et al. 2008. IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 454:350.
72. Okada, Y., Terao, C., Ikari, K. et al. 2012. Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population. Nat. Genet. 44:511.
73. Myouzen, K., Kochi, Y., Shimane, K. et al. 2010. Regulatory polymorphisms in EGR2 are associated with susceptibility to systemic lupus erythematosus. Hum. Mol. Genet. 19:2313.
74. Lopez de Padilla, C. M. and Niewold, T. B. 2016. The type I interferons: Basic concepts and clinical relevance in immune-mediated inflammatory diseases. Gene 576:14.
75. Deng, Y. and Tsao, B. P. 2014. Advances in lupus genetics and epigenetics. Curr. Opin. Rheumatol. 26:482.
76. Liang, Y., Pan, H. F. and Ye, D. Q. 2014. Therapeutic potential of STAT4 in autoimmunity. Expert Opin. Ther. Targets 18:945.
77. Kariuki, S. N., Kirou, K. A., MacDermott, E. J. et al. 2009. Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo. J. Immunol. 182:34.
78. Salloum, R., Franek, B. S., Kariuki, S. N. et al. 2010. Genetic variation at the IRF7/PHRF1 locus is associated with autoantibody profile and serum interferon-alpha activity in lupus patients. Arthritis Rheum. 62:553.
79. Wang, Y., Ewart, D., Crabtree, J. N. et al. 2015. PTPN22 Variant R620W Is Associated With Reduced Toll-like Receptor 7-Induced Type I Interferon in Systemic Lupus Erythematosus. Arthritis Rheumatol. 67:2403.
80. Cho, J. H. and Feldman, M. 2015. Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies. Nat. Med. 21:730.