Familial Risk of Sjögren's Syndrome and Co-aggregation of Autoimmune Diseases in Affected Families: A Nationwide Population Study.
OBJECTIVE
To investigate familial aggregation of Sjögren's syndrome (SS) and the relative risks (RRs) of other autoimmune disease in relatives of patients with SS.


METHODS
We 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.


RESULTS
We 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.


CONCLUSIONS
The 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.
University of Nottingham, Nottingham, UK, and Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
Chang-Fu
CF
Kuo
University of Nottingham, Nottingham, UK.
Matthew J
MJ
Grainge
University of Nottingham, Nottingham, UK.
Ana M
AM
Valdes
Chang Gung University, Taoyuan City, Taiwan.
Lai-Chu
LC
See
Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
Shue-Fen
SF
Luo
Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
Kuang-Hui
KH
Yu
University of Nottingham, Nottingham, UK.
Weiya
W
Zhang
University of Nottingham, Nottingham, UK.
Michael
M
Doherty
D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics; D001327:Autoimmune Diseases / Q000453:epidemiology* / Q000235:genetics*; D015897:Comorbidity; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics; D009157:Myasthenia Gravis / Q000453:epidemiology / Q000235:genetics; D009220:Myositis / Q000453:epidemiology / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000453:epidemiology / Q000235:genetics; D012859:Sjogren's Syndrome / Q000453:epidemiology* / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult