Familial Risk of Sjögren's Syndrome and Co‐aggregation of Autoimmune Diseases in Affected Families: A Nationwide Population Study

Abstract

ObjectiveTo investigate familial aggregation of Sjögren's syndrome (SS) and the relative risks (RRs) of other autoimmune disease in relatives of patients with SS.MethodsWe identified 23,658,577 beneficiaries enrolled in the Taiwan National Health Insurance system in 2010, of whom 12,754 had SS. We identified 21,009,551 parent–child relationships and 17,168,340 pairs of full siblings. The familial risks of SS and other autoimmune diseases, tetrachoric correlation, and familial transmission were estimated.ResultsWe identified 105 patients with SS who had an affected first‐degree relative. The RR of SS was 18.99 (95% confidence interval [95% CI] 9.76–36.93) in siblings of patients with SS, 11.31 (95% CI 8.34–15.33) in offspring, and 12.46 (95% CI 9.34–16.62) in parents. Tetrachoric correlation coefficients were 0.53 (95% CI 0.41–0.65) for cotwins of affected individuals and 0.21 (95% CI 0.16–0.26) for full siblings. The familial transmission (heritability plus shared environmental contribution) was 0.54 (95% CI 0.44–0.77). In first‐degree relatives of patients with SS, the RRs were 2.95 (95% CI 2.33–3.73) for rheumatoid arthritis, 6.25 (95% CI 5.15–7.58) for systemic lupus erythematosus, 2.39 (95% CI 0.77–7.41) for systemic sclerosis, 0.71 (95% CI 0.10–5.07) for idiopathic inflammatory myopathy, 1.97 (95% CI 1.29–3.02) for type 1 diabetes mellitus, 3.38 (95% CI 1.26–9.05) for multiple sclerosis, 1.67 (95% CI 0.83–3.33) for myasthenia gravis, 1.25 (95% CI 1.04–1.50) for psoriasis, 1.21 (95% CI 0.39–3.76) for inflammatory bowel disease, and 2.29 (95% CI 1.19–4.40) for vasculitis.ConclusionThe risk of SS and other autoimmune diseases is increased in relatives of patients with SS, and more than one‐half of phenotypic variance in SS can be explained by familial factors.

Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients: a cross-sectional study from the Big Data Sjögren Project Consortium

“…Genetic and environmental factors probably contribute to phenotypic variance in SjS and a recent study has attributed 54% of the predisposition to developing the disease to familial transmission (heritability plus shared environmental factors) and 46% to non-shared environmental factors 27. Geoepidemiology and ethnicity should be considered as key variables that should be analysed in multi-ethnic studies of patients with primary SjS.…”

Epidemiology of Sjögren’s Syndrome—from an Oral Perspective

“…In a population-based family study of 105 Taiwan patients with SS who had an affected first-degree relative, Kuo et al [86] found a relative risk (RR) for SS in siblings of patients with SS to be 18.99, 11.31 in offspring, and 12.46 in parents. In first-degree relatives of SS patients the RR were 6.25 for having systemic lupus erythematosus, 3.38 for multiple sclerosis and 2.95 for rheumatoid arthritis [86]. …”

Incidence and Mortality of Physician-Diagnosed Primary Sjögren Syndrome

“…The etiology of pSS is not well understood 8 , and probably includes environmental triggers in genetically predisposed subjects, as illustrated by its familial aggregation 9 and predisposing genetic variants 10 . It mainly affects middle-aged females, with a strong sex bias potentially explained by an X chromosome dose effect 11 .…”