Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Family history of rheumatoid arthritis: an old concept with new developments

Key Points

  • Family history of rheumatoid arthritis (RA) is one of the strongest known risk factors for developing RA, conferring twofold to fourfold increased risk in first-degree relatives

  • The heritability of RA seems to be 40%, and is higher for seropositive than for seronegative RA

  • Familial risk does not differ by sex, which suggests that genetic effects do not explain why RA is more common in women than men

  • Family history remains a strong independent predictor of RA onset, despite advances made in identifying genetic risk alleles during the past decade

  • Data so far suggest familial aggregation for treatment response but not for clinical characteristics

Abstract

Family history of rheumatoid arthritis (RA) is a proxy for an individual's genetic and, in part, environmental risk of developing RA, and is a well-recognized predictor of disease onset. Although family history of RA is an old concept, the degree of familial aggregation of RA, whether it differs by age, sex, or serology, and what value it has for clinical decisions once a diagnosis of RA has been made remain unclear. New data have been emerging in parallel to substantial progress made in genetic association studies. In this Review, we describe the various ways that familial aggregation has been measured, and how the findings from these studies, whether they are based on twins, cohorts of first-degree relatives, or genetic data, correspond to each other and aid understanding of the aetiology of RA. In addition, we review the potential usefulness of family history of RA from a clinical point of view, demonstrating that, in the era of big data and genomics, family history still has a role in directing clinical decision-making and research.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Inter-relations of familial risk measures.
Figure 2: Familial risk as a function of heritability and prevalence.
Figure 3: The liability-threshold model.

Similar content being viewed by others

References

  1. Blumberg, B. S. Genetics and rheumatoid arthritis. Arthritis Rheum. 3, 178–185 (1960).

    Article  Google Scholar 

  2. Lawrence, J. S. Heberden Oration, 1969. Rheumatoid arthritis — nature or nurture? Ann. Rheum. Dis. 29, 357–379 (1970).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Batterman, R. C., Grossman, A. J. & Leifer, P. The occurrence of rheumatoid arthritis in twins. Acta Rheumatol. Scand. 2, 161–169 (1956).

    Article  CAS  PubMed  Google Scholar 

  4. Empire Rheumatism Council Scientific Advisory Committee & Lewis-Faning, E. Report on an Enquiry Into the Aetiological Factors Associated with Rheumatoid Arthritis (British Medical Association, 1950).

    Google Scholar 

  5. Miall, W. E. Rheumatoid arthritis in males; an epidemiological study of a Welsh mining community. Ann. Rheum. Dis. 14, 150–158 (1955).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Stecher, R. M. Heredity in joint diseases: the genetics of Heberden's nodes, rheumatoid arthritis, ankylosing spondylitis, rheumatic fever, gout, and osteoarthritis of the hip. Doc. Rheumatol. (1956) 19, 5–74 (1957).

    CAS  Google Scholar 

  7. Neri Serneri, G. G. & Bartoli, V. Heredopathology of reactive mesenchymal disease (so-called collagen disease). I. Research on the hereditary factors in acute primary rheumatism. Acta Genet. Med. Gemellol. (Roma) 5, 155–189 (in Italian) (1956).

    Article  CAS  Google Scholar 

  8. de Blécourt, J. J., Polman, A., de Blécourt-Meindersma, T., Erlee, T. J. D. & Drion, E. F. Hereditary factors in rheumatoid arthritis and ankylosing spondylitis. Ann. Rheum. Dis. 20, 215–223 (1961).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lawrence, J. S. & Ball, J. Genetic studies on rheumatoid arthritis. Ann. Rheum. Dis. 17, 160–168 (1958).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Masi, A. T. & Shulman, L. E. Familial aggregation and rheumatoid disease. Arthritis Rheum. 8, 418–425 (1965).

    Article  CAS  PubMed  Google Scholar 

  11. O'Brien, W. M. The genetics of rheumatoid arthritis. Clin. Exp. Immunol. 2 (Suppl.), 785–802 (1967).

    PubMed Central  Google Scholar 

  12. Bennett, H. & Burch, T. A. The distribution of rheumatoid factor and rheumatoid arthritis in the families of Blackfeet and Pima Indians. Arthritis Rheum. 11, 546–553 (1968).

    Article  CAS  PubMed  Google Scholar 

  13. Burch, T. A., O'Brien, W. M. & Bunim, J. J. Family and genetic studies of rheumatoid arthritis and rheumatoid factor in Blackfeet Indians. Am. J. Public Health Nations Health 54, 1184–1190 (1964).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. O'Brien, W. M., Bennett, P. H., Burch, T. A. & Bunim, J. J. A genetic study of rheumatoid arthritis and rheumatoid factor in Blackfeet and Pima Indians. Arthritis Rheum. 10, 163–179 (1967).

    Article  CAS  PubMed  Google Scholar 

  15. Bunim, J. J., Burch, T. A. & O'Brien, W. M. Influence of genetic and environmental factors on the occurence of rheumatoid arthritis and rheumatoid factor in American Indians. Bull. Rheum. Dis. 15, 349–350 (1964).

    CAS  PubMed  Google Scholar 

  16. Hellgren, L. Inheritance of rheumatoid arthritis. Acta Rheumatol. Scand. 16, 211–216 (1970).

    Article  CAS  PubMed  Google Scholar 

  17. Aho, K., Koskenvuo, M., Tuominen, J. & Kaprio, J. Occurrence of rheumatoid arthritis in a nationwide series of twins. J. Rheumatol. 13, 899–902 (1986).

    CAS  PubMed  Google Scholar 

  18. Silman, A. J. et al. Twin concordance rates for rheumatoid arthritis: results from a nationwide study. Br. J. Rheumatol. 32, 903–907 (1993).

    Article  CAS  PubMed  Google Scholar 

  19. Bellamy, N., Duffy, D., Martin, N. & Mathews, J. Rheumatoid arthritis in twins: a study of aetiopathogenesis based on the Australian Twin Registry. Ann. Rheum. Dis. 51, 588–593 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gregersen, P. K., Silver, J. & Winchester, R. J. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 30, 1205–1213 (1987).

    Article  CAS  PubMed  Google Scholar 

  21. Deighton, C. M. & Walker, D. J. The familial nature of rheumatoid arthritis. Ann. Rheum. Dis. 50, 62–65 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wordsworth, P. & Bell, J. Polygenic susceptibility in rheumatoid arthritis. Ann. Rheum. Dis. 50, 343–346 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wasmuth, A. G., Veale, A. M., Palmer, D. G. & Highton, T. C. Prevalence of rheumatoid arthritis in families. Ann. Rheum. Dis. 31, 85–91 (1972).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Thomas, D. J., Young, A., Gorsuch, A. N., Bottazzo, G. F. & Cudworth, A. G. Evidence for an association between rheumatoid arthritis and autoimmune endocrine disease. Ann. Rheum. Dis. 42, 297–300 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Silman, A. J., Hennessy, E. & Ollier, B. Incidence of rheumatoid arthritis in a genetically predisposed population. Br. J. Rheumatol. 31, 365–368 (1992).

    Article  CAS  PubMed  Google Scholar 

  26. Jones, M. A., Silman, A. J., Whiting, S., Barrett, E. M. & Symmons, D. P. Occurrence of rheumatoid arthritis is not increased in the first degree relatives of a population based inception cohort of inflammatory polyarthritis. Ann. Rheum. Dis. 55, 89–93 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. del Junco, D., Luthra, H. S., Annegers, J. F., Worthington, J. W. & Kurland, L. T. The familial aggregation of rheumatoid arthritis and its relationship to the HLA-DR4 association. Am. J. Epidemiol. 119, 813–829 (1984).

    Article  CAS  PubMed  Google Scholar 

  28. Koumantaki, Y. et al. Family history as a risk factor for rheumatoid arthritis: a case–control study. J. Rheumatol. 24, 1522–1526 (1997).

    CAS  PubMed  Google Scholar 

  29. Grant, S. F. et al. The inheritance of rheumatoid arthritis in Iceland. Arthritis Rheum. 44, 2247–2254 (2001).

    Article  CAS  PubMed  Google Scholar 

  30. Gulcher, J. & Stefansson, K. Population genomics: laying the groundwork for genetic disease modeling and targeting. Clin. Chem. Lab. Med. 36, 523–527 (1998).

    Article  CAS  PubMed  Google Scholar 

  31. Hemminki, K., Li, X., Sundquist, J. & Sundquist, K. Familial associations of rheumatoid arthritis with autoimmune diseases and related conditions. Arthritis Rheum. 60, 661–668 (2009).

    Article  PubMed  Google Scholar 

  32. Somers, E. C., Antonsen, S., Pedersen, L. & Sorensen, H. T. Parental history of lupus and rheumatoid arthritis and risk in offspring in a nationwide cohort study: does sex matter? Ann. Rheum. Dis. 72, 525–529 (2013).

    Article  CAS  PubMed  Google Scholar 

  33. Frisell, T. et al. Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age. Arthritis Rheum. 65, 2773–2782 (2013).

    Article  CAS  PubMed  Google Scholar 

  34. Barrera, P., Radstake, T. R., Albers, J. M., van Riel, P. L. & van de Putte, L. B. Familial aggregation of rheumatoid arthritis in The Netherlands: a cross-sectional hospital-based survey. European Consortium on Rheumatoid Arthritis families (ECRAF). Rheumatology (Oxford) 38, 415–422 (1999).

    Article  CAS  Google Scholar 

  35. Deighton, C. M., Wentzel, J., Cavanagh, G., Roberts, D. F. & Walker, D. J. Contribution of inherited factors to rheumatoid arthritis. Ann. Rheum. Dis. 51, 182–185 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pritchard, M. H. Evidence for a hypothetical non-HLA susceptibility gene in rheumatoid arthritis. Br. J. Rheumatol. 33, 475–479 (1994).

    Article  CAS  PubMed  Google Scholar 

  37. Leu, M., Czene, K. & Reilly, M. Bias correction of estimates of familial risk from population-based cohort studies. Int. J. Epidemiol. 39, 80–88 (2010).

    Article  PubMed  Google Scholar 

  38. Falconer, D. S. Inheritance of liability to certain diseases estimated from incidence among relatives. Ann. Hum. Genet. 29, 51–76 (1965).

    Article  Google Scholar 

  39. Falconer, D. S. & Mackay, T. F. C. Introdution to Quantitative Genetics (Pearson Education Ltd, 1996).

    Google Scholar 

  40. MacGregor, A. J. et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum. 43, 30–37 (2000).

    Article  CAS  PubMed  Google Scholar 

  41. Haj Hensvold, A. et al. Environmental and genetic factors in the development of anticitrullinated protein antibodies (ACPAs) and ACPA-positive rheumatoid arthritis: an epidemiological investigation in twins. Ann. Rheum. Dis. http://dx.doi.org/10.1136/annrheumdis-2013-203947 (2013).

  42. Svendsen, A. J., Holm, N. V., Kyvik, K., Petersen, P. H. & Junker, P. Relative importance of genetic effects in rheumatoid arthritis: historical cohort study of Danish nationwide twin population. BMJ 324, 264–266 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Svendsen, A. J. et al. On the origin of rheumatoid arthritis: the impact of environment and genes — a population based twin study. PLoS ONE 8, e57304 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Silman, A. J. Commentary: do genes or environment influence development of rheumatoid arthritis? BMJ 324, 264 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  45. MacGregor, A. J., Lanchbury, J., Rigby, A. S., Kaprio, J. & Snieder, H. Using twin studies to label disease as genetic or environmental is inappropriate. BMJ 324, 1100 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Sugiyama, D. et al. Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of observational studies. Ann. Rheum. Dis. 69, 70–81 (2010).

    Article  CAS  PubMed  Google Scholar 

  47. Di Giuseppe, D., Alfredsson, L., Bottai, M., Askling, J. & Wolk, A. Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study. BMJ 345, e4230 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kallberg, H. et al. Alcohol consumption is associated with decreased risk of rheumatoid arthritis: results from two Scandinavian case–control studies. Ann. Rheum. Dis. 68, 222–227 (2009).

    Article  CAS  PubMed  Google Scholar 

  49. Jiang, X. et al. To what extent is the familial risk of rheumatoid arthritis explained by established rheumatoid arthritis risk factors? Arthritis Rheumatol. 67, 352–362 (2015).

    Article  CAS  PubMed  Google Scholar 

  50. Polderman, T. J. et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat. Genet. 47, 702–709 (2015).

    Article  CAS  PubMed  Google Scholar 

  51. Khoury, M. J., Beaty, T. H. & Liang, K. Y. Can familial aggregation of disease be explained by familial aggregation of environmental risk factors? Am. J. Epidemiol. 127, 674–683 (1988).

    Article  CAS  PubMed  Google Scholar 

  52. Okada, Y. et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506, 376–381 (2014).

    Article  CAS  PubMed  Google Scholar 

  53. Stahl, E. A. et al. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis. Nat. Genet. 44, 483–489 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yang, J., Lee, S. H., Goddard, M. E. & Visscher, P. M. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76–82 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lee, S. H. et al. New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis. Int. J. Epidemiol. 44, 1706–1721 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Han, B. et al. 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, 522–532 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Padyukov, L. et al. A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis. Ann. Rheum. Dis. 70, 259–265 (2011).

    Article  PubMed  Google Scholar 

  58. de Blécourt, J. J., Boerma, F. W. & Vorenkamp, E. O. Rheumatoid arthritis (R.A.) factor in near relatives of sero-positive and sero-negative patients with rheumatoid arthritis. Ann. Rheum. Dis. 21, 339–341 (1962).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Wolfe, F., Kleinheksel, S. M. & Khan, M. A. Prevalence of familial occurrence in patients with rheumatoid arthritis. Br. J. Rheumatol. 27 (Suppl. 2), 150–152 (1988).

    Article  PubMed  Google Scholar 

  60. Laivoranta-Nyman, S. et al. Immunogenetic differences between patients with familial and non-familial rheumatoid arthritis. Ann. Rheum. Dis. 59, 173–177 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Radstake, T. R. et al. Familial versus sporadic rheumatoid arthritis (RA). A prospective study in an early RA inception cohort. Rheumatology (Oxford) 39, 267–273 (2000).

    Article  CAS  Google Scholar 

  62. Radstake, T. R. et al. Genetic anticipation in rheumatoid arthritis in Europe. European Consortium on Rheumatoid Arthritis Families. J. Rheumatol. 28, 962–967 (2001).

    CAS  PubMed  Google Scholar 

  63. de Vries, R. Genetics of rheumatoid arthritis: time for a change! Curr. Opin. Rheumatol. 23, 227–232 (2011).

    Article  CAS  PubMed  Google Scholar 

  64. Kurko, J. et al. Genetics of rheumatoid arthritis — a comprehensive review. Clin. Rev. Allergy Immunol. (2013).

  65. van der Woude, D. et al. Quantitative heritability of anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis. Arthritis Rheum. 60, 916–923 (2009).

    Article  PubMed  Google Scholar 

  66. Frisell, T. et al. Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case–control study in Sweden. Ann. Rheum. Dis. 75, 183–189 (2016).

    Article  PubMed  Google Scholar 

  67. Frisell, T., Saevarsdottir, S. & Askling, J. Does a family history of RA influence the clinical presentation and treatment response in RA? Ann. Rheum. Dis. http://dx.doi.org/10.1136/annrheumdis-2015-207670 (2015).

  68. Sparks, J. A. et al. Contributions of familial rheumatoid arthritis or lupus and environmental factors to risk of rheumatoid arthritis in women: a prospective cohort study. Arthritis Care Res. (Hoboken) 66, 1438–1446 (2014).

    Article  Google Scholar 

  69. Sparks, J. A. et al. Improved performance of epidemiologic and genetic risk models for rheumatoid arthritis serologic phenotypes using family history. Ann. Rheum. Dis. 74, 1522–1529 (2014).

    Article  PubMed  Google Scholar 

  70. van Beers, J. J. et al. ACPA fine-specificity profiles in early rheumatoid arthritis patients do not correlate with clinical features at baseline or with disease progression. Arthritis Res. Ther. 15, R140 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Jiang, X. et al. Anti-CarP antibodies in two large cohorts of patients with rheumatoid arthritis and their relationship to genetic risk factors, cigarette smoking and other autoantibodies. Ann. Rheum. Dis. 73, 1761–1768 (2014).

    Article  CAS  PubMed  Google Scholar 

  72. Eyre, S. et al. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat. Genet. 44, 1336–1340 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Stahl, E. A. et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat. Genet. 42, 508–514 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Bowes, J. & Barton, A. Recent advances in the genetics of RA susceptibility. Rheumatology (Oxford) 47, 399–402 (2008).

    Article  CAS  Google Scholar 

  75. Raychaudhuri, S. et al. Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nat. Genet. 40, 1216–1223 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Deighton, C. M., Walker, D. J., Griffiths, I. D. & Roberts, D. F. The contribution of HLA to rheumatoid arthritis. Clin. Genet. 36, 178–182 (1989).

    Article  CAS  PubMed  Google Scholar 

  77. Hasstedt, S. J., Clegg, D. O., Ingles, L. & Ward, R. H. HLA-linked rheumatoid arthritis. Am. J. Hum. Genet. 55, 738–746 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Raychaudhuri, S. et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat. Genet. 44, 291–296 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Thompson, A. E. et al. Comprehensive arthritis referral study — phase 2: analysis of the comprehensive arthritis referral tool. J. Rheumatol. 41, 1980–1989 (2014).

    Article  PubMed  Google Scholar 

  80. Larkin, J. G. Family history of rheumatoid arthritis — a non-predictor of inflammatory disease? Rheumatology (Oxford) 49, 608–609 (2010).

    Article  Google Scholar 

  81. Cardenas-Roldan, J., Rojas-Villarraga, A. & Anaya, J. M. How do autoimmune diseases cluster in families? A systematic review and meta-analysis. BMC Med. 11, 73 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Deighton, C. M., Roberts, D. F. & Walker, D. J. Effect of disease severity on rheumatoid arthritis concordance in same sexed siblings. Ann. Rheum. Dis. 51, 943–945 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Wolfe, F., Kleinheksel, S. M. & Khan, M. A. Familial versus sporadic rheumatoid arthritis: a comparison of the demographic and clinical characteristics of 956 patients. J. Rheumatol. 15, 400–404 (1988).

    CAS  PubMed  Google Scholar 

  84. Silman, A. J., Ollier, W. E. & Currey, H. L. Failure to find disease similarity in sibling pairs with rheumatoid arthritis. Ann. Rheum. Dis. 46, 135–138 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Deighton, C. M. & Walker, D. J. What factors distinguish probands from multicase rheumatoid arthritis same sex sibships from sporadic disease? J. Rheumatol. 19, 237–241 (1992).

    CAS  PubMed  Google Scholar 

  86. Balsa, A. et al. Clinical and immunogenetic characteristics of European multicase rheumatoid arthritis families. Ann. Rheum. Dis. 60, 573–576 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Jarvinen, P., Koskenvuo, M., Koskimies, S., Kotaniemi, K. & Aho, K. Rheumatoid arthritis in identical twins: a clinical and immunogenetic study of eight concordant pairs derived from a nationwide twin panel. Scand. J. Rheumatol. 20, 159–164 (1991).

    Article  CAS  PubMed  Google Scholar 

  88. Jawaheer, D., Lum, R. F., Amos, C. I., Gregersen, P. K. & Criswell, L. A. Clustering of disease features within 512 multicase rheumatoid arthritis families. Arthritis Rheum. 50, 736–741 (2004).

    Article  PubMed  Google Scholar 

  89. Cui, J. et al. The influence of polygenic risk scores on heritability of anti-CCP level in RA. Genes Immun. 15, 107–114 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Rojas-Villarraga, A. et al. Familial disease, the HLA-DRB1 shared epitope and anti-CCP antibodies influence time at appearance of substantial joint damage in rheumatoid arthritis. J. Autoimmun. 32, 64–69 (2009).

    Article  CAS  PubMed  Google Scholar 

  91. Knevel, R. et al. Genetic predisposition of the severity of joint destruction in rheumatoid arthritis: a population-based study. Ann. Rheum. Dis. 71, 707–709 (2012).

    Article  PubMed  Google Scholar 

  92. Umicevic Mirkov, M. et al. Estimation of heritability of different outcomes for genetic studies of TNFi response in patients with rheumatoid arthritis. Ann. Rheum. Dis. 74, 2183–2187 (2014).

    Article  CAS  PubMed  Google Scholar 

  93. Plant, D., Wilson, A. G. & Barton, A. Genetic and epigenetic predictors of responsiveness to treatment in RA. Nat. Rev. Rheumatol. 10, 329–337 (2014).

    Article  CAS  PubMed  Google Scholar 

  94. McGue, M. When assessing twin concordance, use the probandwise not the pairwise rate. Schizophr. Bull. 18, 171–176 (1992).

    Article  CAS  PubMed  Google Scholar 

  95. Fischer, R. The correlation between relatives on the supposition of Mendelian inheritance. Trans. R.Soc. Edinb. 52, 399–433 (1918).

    Article  Google Scholar 

  96. Visscher, P. M., Hill, W. G. & Wray, N. R. Heritability in the genomics era — concepts and misconceptions. Nat. Rev. Genet. 9, 255–266 (2008).

    Article  CAS  PubMed  Google Scholar 

  97. Todorov, A. A. & Suarez, B. K. Genetic liability model. Encyclopedia of Biostatistics (John Wiley & Sons, 2005).

    Google Scholar 

  98. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007).

  99. Tsonaka, R., van der Woude, D. & Houwing-Duistermaat, J. Marginal genetic effects estimation in family and twin studies using random-effects models. Biometrics 71, 1130–1138 (2015).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

T.F. researched data for the article, J.A. and T.F. wrote the article, and all authors made substantial contributions to discussions of the content and review/editing of the manuscript before submission.

Corresponding author

Correspondence to Johan Askling.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Frisell, T., Saevarsdottir, S. & Askling, J. Family history of rheumatoid arthritis: an old concept with new developments. Nat Rev Rheumatol 12, 335–343 (2016). https://doi.org/10.1038/nrrheum.2016.52

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrrheum.2016.52

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing