Skip to main content
SpringerLink
Log in

Does Genetics Play a Role in Auto-immune Diseases?

  • Chapter
  • First Online:
Women's Health in Autoimmune Diseases

  • 433 Accesses

Abstract

Eighty autoimmune diseases (AD) have been identified to date, and they affect 5–10% of the population. Familial clustering is evident in many autoimmune conditions. A higher concordance of disease association is seen among monozygotic twins as compared to dizygotic twins and other siblings. With advances in genetic diagnostic facilities, a variety of genetic studies have been developed which have established genetic associations with AD. This chapter aims at providing an overview of the genetic profile of AD and the main determinants which define the ultimate phenotypic manifestations of the genetic variants related to AD.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Jacobson DL, Gange SJ, Rose NR, Graham NM (1997) Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol 84(3):223–243

    CAS  PubMed  Google Scholar 

  2. Dai Y, Zhang L, Hu C, Zhang Y (2010) Genome-wide analysis of histone H3 lysine 4 trimethylation by ChIP-chip in peripheral blood mononuclear cells of systemic lupus erythematosus patients. Clin Exp Rheumatol 28(2):158–168

    CAS  PubMed  Google Scholar 

  3. Barreiro LB, Quintana-Murci L (2010) From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat Rev Genet 11(1):17–30

    CAS  PubMed  Google Scholar 

  4. Zhernakova A, Elbers CC, Ferwerda B, Romanos J, Trynka G, Dubois PC et al (2010) Evolutionary and functional analysis of celiac risk loci reveals SH2B3 as a protective factor against bacterial infection. Am J Hum Genet 86(6):970–977

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Ramos PS, Shaftman SR, Ward RC, Langefeld CD (2014) Genes associated with SLE are targets of recent positive selection. Autoimmune Dis 2014:203435. [cited 6 Mar 2019]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920976/

    PubMed  PubMed Central  Google Scholar 

  6. Autoimmune Statistics. The Autoimmune Registry. [cited 10 Mar 2019]. Available from: http://www.autoimmuneregistry.org/autoimmune-statistics

  7. Autoimmune Disease Statistics•AARDA (2016) AARDA. [cited 10 Mar 2019]. Available from: https://www.aarda.org/news-information/statistics/

  8. Women & Autoimmunity•AARDA (2016) AARDA. [cited 10 Mar 2019]. Available from: https://www.aarda.org/who-we-help/patients/women-and-autoimmunity/

  9. (PDF) The world incidence and prevalence of autoimmune diseases is increasing. ResearchGate. [cited 10 Mar 2019]. Available from: https://www.researchgate.net/publication/294419057_The_World_Incidence_and_Prevalence_of_Autoimmune_Diseases_is_Increasing

  10. Torfs CP, King MC, Huey B, Malmgren J, Grumet FC (1986) Genetic interrelationship between insulin-dependent diabetes mellitus, the autoimmune thyroid diseases, and rheumatoid arthritis. Am J Hum Genet 38(2):170–187

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Eaton WW, Rose NR, Kalaydjian A, Pedersen MG, Mortensen PB (2007) Epidemiology of autoimmune diseases in Denmark. J Autoimmun 29(1):1–9

    PubMed  PubMed Central  Google Scholar 

  12. Somers EC, Thomas SL, Smeeth L, Hall AJ (2006) Autoimmune diseases co-occurring within individuals and within families: a systematic review. Epidemiol Camb Mass 17(2):202–217

    Google Scholar 

  13. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921

    CAS  Google Scholar 

  14. Ezkurdia I, Juan D, Rodriguez JM et al (2014) Multiple evidence strands suggest that there may be as few as 19,000 human protein-coding genes. Hum Mol Genet. 23(22):5866–5878. https://doi.org/10.1093/hmg/ddu309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bagshaw ATM (2017) Functional mechanisms of microsatellite DNA in eukaryotic genomes. Genome Biol Evol 9(9):2428–2443

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Charlon T, Martínez-Bueno M, Bossini-Castillo L, Carmona FD, Cara AD, Wojcik J et al (2016) Single nucleotide polymorphism clustering in systemic autoimmune diseases. PLoS One 11(8):e0160270

    PubMed  PubMed Central  Google Scholar 

  17. Patnala R, Clements J, Batra J (2013) Candidate gene association studies: a comprehensive guide to useful in silico tools. BMC Genet 14:39

    CAS  PubMed  PubMed Central  Google Scholar 

  18. FutureLearn. The applications of genetic linkage and association analysis. FutureLearn. [cited 18 Mar 2019]. Available from: https://www.futurelearn.com/courses/translational-research/0/steps/14199

  19. Tomer Y, Ban Y, Concepcion E, Barbesino G, Villanueva R, Greenberg DA et al (2003) Common and unique susceptibility loci in graves and hashimoto diseases: results of whole-genome screening in a data set of 102 multiplex families. Am J Hum Genet 73(4):736–747

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J et al (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411(6837):599–603

    CAS  PubMed  Google Scholar 

  21. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R et al (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411(6837):603–606

    CAS  Google Scholar 

  22. Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW et al (2007) STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med 357(10):977–986

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang MH, Cordell HJ, Van Steen K (2019) Statistical methods for genome-wide association studies. Semin Cancer Biol. 55:53–60. https://doi.org/10.1016/j.semcancer.2018.04.008

    Article  PubMed  Google Scholar 

  24. Visscher PM, Wray NR, Zhang Q, Sklar P, McCarthy MI, Brown MA et al (2017) 10 Years of GWAS discovery: biology, function, and translation. Am J Hum Genet 101(1):5–22

    CAS  PubMed  PubMed Central  Google Scholar 

  25. McDevitt HO, Bodmer WF (1974) HL-A, immune-response genes, and disease. Lancet 303(7869):1269–1275

    Google Scholar 

  26. The MHC Sequencing Consortium (1999) Complete sequence and gene map of a human major histocompatibility complex. Nature 401(6756):921–923

    Google Scholar 

  27. Castiblanco J, Arcos-Burgos M, Anaya J-M (2013) Introduction to genetics of autoimmune diseases. El Rosario University Press, Bogota. [cited 10 May 2019]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459433/

  28. Wolters VM, Wijmenga C (2008) Genetic background of celiac disease and its clinical implications. Am J Gastroenterol 103(1):190–195

    PubMed  Google Scholar 

  29. Gutierrez-Achury J, Zhernakova A, Pulit SL, Trynka G, Hunt KA, Romanos J et al (2015) Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease. Nat Genet 47(6):577–578

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Pallav K, Kabbani T, Tariq S, Vanga R, Kelly CP, Leffler DA (2014) Clinical utility of celiac disease-associated HLA testing. Dig Dis Sci 59(9):2199–2206

    PubMed  PubMed Central  Google Scholar 

  31. Thomson G, Valdes AM, Noble JA, Kockum I, Grote MN, Najman J et al (2007) Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis. Tissue Antigens 70(2):110–127

    CAS  PubMed  Google Scholar 

  32. Koeleman BPC, Lie BA, Undlien DE, Dudbridge F, Thorsby E, de Vries RRP et al (2004) Genotype effects and epistasis in type 1 diabetes and HLA-DQ trans dimer associations with disease. Genes Immun 5(5):381–388

    CAS  PubMed  Google Scholar 

  33. Corper AL, Stratmann T, Apostolopoulos V, Scott CA, Garcia KC, Kang AS et al (2000) A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes. Science 288(5465):505–511

    CAS  PubMed  Google Scholar 

  34. Gregersen PK, Silver J, Winchester RJ (1987) The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 30(11):1205–1213

    CAS  PubMed  Google Scholar 

  35. Mackie SL, Taylor JC, Martin SG, YEAR Consortium, UKRAG Consortium, Wordsworth P et al (2012) A spectrum of susceptibility to rheumatoid arthritis within HLA-DRB1: stratification by autoantibody status in a large UK population. Genes Immun 13(2):120–128

    CAS  PubMed  Google Scholar 

  36. Zanelli E, Breedveld FC, de Vries RR (2000) HLA class II association with rheumatoid arthritis: facts and interpretations. Hum Immunol 61(12):1254–1261

    CAS  PubMed  Google Scholar 

  37. Auger I, Toussirot E, Roudier J (1997) Molecular mechanisms involved in the association of HLA-DR4 and rheumatoid arthritis. Immunol Res 16(1):121–126

    CAS  PubMed  Google Scholar 

  38. Newton JL, Harney SMJ, Wordsworth BP, Brown MA (2004) A review of the MHC genetics of rheumatoid arthritis. Genes Immun 5(3):151–157

    CAS  PubMed  Google Scholar 

  39. Weyand CM, Goronzy JJ (2000) Association of MHC and rheumatoid arthritis:HLA polymorphisms in phenotypic variants of rheumatoid arthritis. Arthritis Res 2(3):212–216

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Kampstra ASB, Toes REM (2017) HLA class II and rheumatoid arthritis: the bumpy road of revelation. Immunogenetics 69(8):597–603

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Cruz-Tapias P, Pérez-Fernández OM, Rojas-Villarraga A, Rodríguez-Rodríguez A, Arango M-T, Anaya J-M (2012) Shared HLA class II in six autoimmune diseases in Latin America: a meta-analysis. Autoimmun Dis 2012:569728. [cited 20 Mar 2019]. Available from: https://www.hindawi.com/journals/ad/2012/569728/

    Google Scholar 

  42. Stamatelos P, Anagnostouli MC (2017) HLA-genotype in multiple sclerosis: the role in disease onset, clinical course, cognitive status and response to treatment: a clear step towards personalized therapeutics

    Google Scholar 

  43. Niu Z, Zhang P, Tong Y (2015) Value of HLA-DR genotype in systemic lupus erythematosus and lupus nephritis: a meta-analysis. Int J Rheum Dis 18:17–28. https://doi.org/10.1111/1756-185X.12528

  44. Buxton SE, Benjamin RJ, Clayberger C, Parham P, Krensky AM (1992) Anchoring pockets in human histocompatibility complex leukocyte antigen (HLA) class I molecules: analysis of the conserved B (“45”) pocket of HLA-B27. J Exp Med 175(3):809–820

    CAS  PubMed  Google Scholar 

  45. Cortes A, Pulit SL, Leo PJ et al (2015) Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1. Nat Commun 6, 7146 . Published 2015 May 21. https://doi.org/10.1038/ncomms8146

  46. Nakken B, Jonsson R, Brokstad KA, Omholt K, Nerland AH, Haga HJ et al (2001) Associations of MHC class II alleles in Norwegian primary Sjögren’s syndrome patients: implications for development of autoantibodies to the Ro52 autoantigen. Scand J Immunol 54(4):428–433

    CAS  PubMed  Google Scholar 

  47. Li L, Chen S, Wen X, Wang Q, Lv G, Li J et al (2017) Positive association between ANKRD55 polymorphism 7731626 and dermatomyositis/polymyositis with interstitial lung disease in Chinese Han population. Biomed Res Int 2017:2905987. [cited 11 Mar 2019]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392395/

    PubMed  PubMed Central  Google Scholar 

  48. Umapathy S, Pawar A, Mitra R, Khuperkar D, Devaraj JP, Ghosh K et al (2011) HLA-A and HLA-B alleles associated in psoriasis patients from Mumbai, Western India. Indian J Dermatol 56(5):497–500

    PubMed  PubMed Central  Google Scholar 

  49. Díaz-Peña R, López-Vázquez A, López-Larrea C (2012) Old and new HLA associations with ankylosing spondylitis. Tissue Antigens 80(3):205–213

    PubMed  Google Scholar 

  50. Weinstock C, Matheis N, Barkia S, Haager M-C, Janson A, Marković A et al (2011) Autoimmune polyglandular syndrome type 2 shows the same HLA class II pattern as type 1 diabetes. Tissue Antigens 77(4):317–324

    CAS  PubMed  Google Scholar 

  51. Sollid LM, Markussen G, Ek J, Gjerde H, Vartdal F, Thorsby E (1989) Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer. J Exp Med 169(1):345–350

    CAS  PubMed  Google Scholar 

  52. Tsuchiya N (2013) Genetics of ANCA-associated vasculitis in Japan: a role for HLA-DRB1∗09:01 haplotype. Clin Exp Nephrol. 17(5):628–630. https://doi.org/10.1007/s10157-012-0691-6

  53. Pradhan V, Borse V, Ghosh K (2010) PTPN22 gene polymorphisms in autoimmune diseases with special reference to systemic lupus erythematosus disease susceptibility. J Postgrad Med 56(3):239–242

    CAS  PubMed  Google Scholar 

  54. Buckner J. Linking genetic variation in the PTPN2 gene to autoimmune disease susceptibility. Benaroya Research Institute at Virginia Mason, Seattle, WA. [cited 20 Mar 2019]. Available from: http://grantome.com/grant/NIH/R03-DA027013-01

  55. Walker LSK (2015) CTLA-4 and autoimmunity: new twists in the tale. Trends Immunol 36(12):760–762

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Rae W, Ward D, Mattocks CJ, Gao Y, Pengelly RJ, Patel SV et al (2017) Autoimmunity/inflammation in a monogenic primary immunodeficiency cohort. Clin Transl Immunol 6(9):e155

    Google Scholar 

  57. Okada Y, Kim K, Han B, Pillai NE, Ong RT-H, Saw W-Y et al (2014) Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations. Hum Mol Genet 23(25):6916–6926

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Primary immunodeficiency association with systemic lupus erythematosus: review of literature and lessons learned by the Rheumatology Division of a tertiary university hospital at São Paulo, Brazil | Elsevier Enhanced Reader. [cited 23 May 2019]. Available from: https://reader.elsevier.com/reader/sd/pii/S2255502115000644?token=BB8776B4DBE7920B2CF2DDD653DBBBC3B3CEDB72E7FE26C45C80F31B8DD2A34C4A17792CB9367E7BFFC829357FEDD0AB

  59. Jesus AA, Liphaus BL, Silva CA, Bando SY, Andrade LEC, Coutinho A et al (2011) Complement and antibody primary immunodeficiency in juvenile systemic lupus erythematosus patients. Lupus 20(12):1275–1284

    CAS  PubMed  Google Scholar 

  60. Grimbacher B, Warnatz K, Yong PFK, Korganow A-S, Peter H-H (2016) The crossroads of autoimmunity and immunodeficiency: Lessons from polygenic traits and monogenic defects. J Allergy Clin Immunol 137(1):3–17

    CAS  PubMed  Google Scholar 

  61. Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L et al (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27(1):20–21

    CAS  PubMed  Google Scholar 

  62. Solovieff N, Cotsapas C, Lee PH, Purcell SM, Smoller JW (2013) Pleiotropy in complex traits: challenges and strategies. Nat Rev Genet 14(7):483–495

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Ahmad T, Marshall SE, Jewell D (2006) Genetics of inflammatory bowel disease: the role of the HLA complex. World J Gastroenterol 12(23):3628–3635

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Allannic H, Fauchet R, Lorcy Y, Heim J, Gueguen M, Leguerrier AM et al (1980) HLA and Graves’ disease: an association with HLA-DRw3. J Clin Endocrinol Metab 51(4):863–867

    CAS  PubMed  Google Scholar 

  65. Goudey B, Abraham G, Kikianty E, Wang Q, Rawlinson D, Shi F et al (2017) Interactions within the MHC contribute to the genetic architecture of celiac disease. PLoS One 12(3):e0172826

    PubMed  PubMed Central  Google Scholar 

  66. Wei JC et al (2015) Interaction between HLA-B60 and HLA-B27 as a better predictor of ankylosing spondylitis in a Taiwanese population. PLoS One 10:e0137189. [cited 20 Mar 2019]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26469786

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Allergy Immunology Unit, Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Himanshi Chaudhary, Amit Rawat & Surjit Singh

Authors
  1. Himanshi Chaudhary
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amit Rawat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Surjit Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Internal Medicine, PGIMER, Chandigarh, India

    Shefali Khanna Sharma

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chaudhary, H., Rawat, A., Singh, S. (2020). Does Genetics Play a Role in Auto-immune Diseases?. In: Sharma, S. (eds) Women's Health in Autoimmune Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-15-0114-2_1

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-0114-2_1

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-0113-5

  • Online ISBN: 978-981-15-0114-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation