Familial aggregation and heritability of ankylosing spondylitis – a Swedish nested case–control study

Abstract

Objectives AS is known to be a highly heritable disease, but previous studies on the magnitude of the familial aggregation and heritability of AS have been small and inconclusive, with familial relative risks ranging from 17 to 94. We aimed to improve estimates of these factors by studying families of all subjects diagnosed with AS in Sweden over a period of 16 years and to investigate if familial risks vary by sex or type of relative. Methods In a nested case–control study, we identified AS index patients from the National Patient Register (NPR) and the Swedish Rheumatology Quality Register (SRQ) between 2001 and 2016. Each index patient was matched on age and sex to up to 50 general population controls. First-degree relatives of index patients and controls were identified through the Multi-Generation Register, with disease status ascertained in the NPR and SRQ. Familial risks were defined as odds ratios (ORs) of having AS when exposed to a first-degree relative with AS, using conditional logistic regression. Results The overall familial OR for AS was 19.4 (95% CI 18.1, 20.8). Estimates were similar for different relative types and by sex, but having more than one affected relative resulted in a higher risk [OR 68.0 (95% CI 51.3, 90.1)]. Heritability, estimated by assuming sibling risks were completely due to genetics, was 77% (95% CI 73, 80). Conclusion Although the familial risk and heritability of AS are higher than for most other diseases, we report estimates that are substantially lower than commonly referenced numbers for AS from other populations.

What Have We Learned From Family-Based Studies About Spondyloarthritis?

“…However, similar ratios were obtained in population-based studies in Iceland with a first-degree RRR ranging from 75 to 94 (Thjodleifsson et al, 2007;Geirsson et al, 2010). In contrast, two register-based case-control studies of AS patients in Sweden reported a substantially lower RRR with a sibling risk between 15 and 20 (Sundquist et al, 2008;Morin et al, 2019).…”

Is family history a predictor of response to tumour necrosis factor inhibitors in spondyloarthritis? A Swedish nationwide cohort study

“…A distinctive feature of SpA is the high familial aggregation. We found a 20-fold increased risk of ankylosing spondylitis (AS) in first-degree relatives of AS patients (17), and even higher estimates have been reported (18)(19)(20). In psoriatic arthritis (PsA), 30-55 times higher risks are reported in first-degree relatives (21)(22)(23)(24).…”

A Road Map of the Axial Spondyloarthritis Continuum

“…16 In a study of all patients diagnosed with r-axSpA in Sweden during a 16-year period, the overall familial odds ratio (OR) for r-axSpA was 19.4 (95% CI, 18.1 to 20.8), and patients with more than 1 family member with r-axSpA had a higher risk for development of the disease (OR, 60.8; 95% CI, 51.3 to 90.1) compared with patients with no known family history. 17 Several genetic risk factors have been associated with the development of axSpA. Among these, the presence of the genetic marker HLA-B27 is consistently and strongly associated with development of axSpA.…”