Family history of systemic lupus erythematosus and risk of autoimmune disease: Nationwide Cohort Study in Denmark 1977-2013.
To provide population-based estimates of relative risk of SLE and other autoimmune diseases (ADs) in relatives of SLE patients.



A cohort of 5 237 319 Danish residents identified through the Civil Registration System was coupled to their relatives through the parental link and followed for SLE and other ADs between 1977 and 2013 through linkage to the National Patient Register. Twin zygosity was established through the Danish Twin Registry. Hazard ratios (HRs) with 95% CIs were calculated using Cox proportional hazards regression analyses.



During 117.5 million person-years of follow-up, 3612 persons were hospitalized with SLE. HRs of SLE were high among first-degree (HR = 10.3; 95% CI: 8.25, 12.9; n = 80) and second- or third-degree relatives of SLE patients (HR = 3.60; 95% CI: 2.20, 5.90; n = 16). HRs for any AD were elevated in first-degree (HR = 1.51; 95% CI: 1.41, 1.62; n = 785) and second- or third-degree relatives of SLE patients (HR = 1.28; 95% CI: 1.18, 1.39; n = 582). Among individuals with SLE-affected first-degree relatives, the risk was significantly increased for RA (HR = 1.64; 95% CI: 1.35, 1.99; n = 103), IBD (HR = 1.21; 95% CI: 1.02, 1.43; n = 130) and type 1 diabetes mellitus (HR = 1.23; 95% CI: 1.01, 1.48; n = 106). Risk of other ADs was significantly increased both among SLE-affected first-degree (HR = 2.08; 95% CI: 1.88, 2.31; n = 371) and second- or third-degree relatives (HR = 1.38; 95% CI: 1.23, 1.54; n = 313).



Family history of SLE is associated with a clearly elevated risk of SLE and, to a much lesser degree, of RA and other ADs.
Copenhagen Lupus and Vasculitis Clinic, Centre for Rheumatology and Spine Diseases, Rigshospitalet.
Constance Jensina
CJ
Ulff-Møller
Department of Epidemiology Research, Statens Serum Institut, Copenhagen.
Jacob
J
Simonsen
Department of Clinical Research and the Danish Twin Registry, EBB, University of Southern Denmark.|Odense Patient data Explorative Network (OPEN), Odense University Hospital, J.B. Winsløws Odense C, Denmark.
Kirsten Ohm
KO
Kyvik
Copenhagen Lupus and Vasculitis Clinic, Centre for Rheumatology and Spine Diseases, Rigshospitalet.
Søren
S
Jacobsen
Department of Epidemiology Research, Statens Serum Institut, Copenhagen.
Morten
M
Frisch
D001327:Autoimmune Diseases / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D010375:Pedigree; D012042:Registries; D012307:Risk Factors
autoimmune disease; cohort study; epidemiology; familial aggregation; familial risk; systemic lupus erythematosus