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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.

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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.

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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.

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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

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