L R Ginn1, J P Lin, P H Plotz, S J Bale, R L Wilder, A Mbauya, F W Miller. 1. Center for Biologics Evaluation and Research, US Food and Drug Administration, and National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract
OBJECTIVE: To test the hypothesis that many autoimmune diseases share common genetic risk factors and to define the frequency and distribution of autoimmune diseases in relatives of patients with very rare disorders, the idiopathic inflammatory myopathies (IIM). METHODS: We evaluated, in a prospective case-control study, consecutive patients with IIM who were referred to our center and ascertained without regard to family history or known risk factors for autoimmunity, and all available family members. We used a standardized assessment to determine the presence and type of autoimmune disease in each subject. A matched comparison group of control subjects without autoimmune disease who were referred to our center and their families were similarly assessed. RESULTS: Autoimmune diseases were significantly increased in prevalence (21.9%) in the 151 first-degree relatives of the 21 IIM probands compared with the prevalence (4.9%) in the 143 relatives of the 21 control probands (odds ratio [OR] by regression analysis 7.9, 95% confidence interval [95% CI] 2.9-21.9, P < 0.001). Women had more autoimmune disease than men (OR by regression analysis 4.6, 95% CI 2.3-9.0) and the odds ratio for autoimmune disease increased 0.02 per year of age. These disorders tended to follow the frequency distribution of autoimmune diseases in the general population. Genetic modeling studies showed that a non-Mendelian polygenic inheritance pattern for autoimmune disease was most consistent with these data. CONCLUSION: Autoimmune diseases are significantly increased in frequency in first-degree relatives of IIM patients, affect more women than men, increase with age, and are distributed in a pattern similar to that in the general population. Many autoimmune disorders share genes that together act as polygenic risk factors for autoimmunity.
OBJECTIVE: To test the hypothesis that many autoimmune diseases share common genetic risk factors and to define the frequency and distribution of autoimmune diseases in relatives of patients with very rare disorders, the idiopathic inflammatory myopathies (IIM). METHODS: We evaluated, in a prospective case-control study, consecutive patients with IIM who were referred to our center and ascertained without regard to family history or known risk factors for autoimmunity, and all available family members. We used a standardized assessment to determine the presence and type of autoimmune disease in each subject. A matched comparison group of control subjects without autoimmune disease who were referred to our center and their families were similarly assessed. RESULTS:Autoimmune diseases were significantly increased in prevalence (21.9%) in the 151 first-degree relatives of the 21 IIM probands compared with the prevalence (4.9%) in the 143 relatives of the 21 control probands (odds ratio [OR] by regression analysis 7.9, 95% confidence interval [95% CI] 2.9-21.9, P < 0.001). Women had more autoimmune disease than men (OR by regression analysis 4.6, 95% CI 2.3-9.0) and the odds ratio for autoimmune disease increased 0.02 per year of age. These disorders tended to follow the frequency distribution of autoimmune diseases in the general population. Genetic modeling studies showed that a non-Mendelian polygenic inheritance pattern for autoimmune disease was most consistent with these data. CONCLUSION:Autoimmune diseases are significantly increased in frequency in first-degree relatives of IIM patients, affect more women than men, increase with age, and are distributed in a pattern similar to that in the general population. Many autoimmune disorders share genes that together act as polygenic risk factors for autoimmunity.
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