Chang-Fu Kuo1,2, Matthew J Grainge3, Ana M Valdes1, Lai-Chu See4,5, Kuang-Hui Yu2, S W Steven Shaw6,7, Shue-Fen Luo2,7, Weiya Zhang1, Michael Doherty1. 1. Academic Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK. 2. Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 3. Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK. 4. Department of Public Health, College of Medicine. 5. Biostatistics Core Laboratory, Molecular Medicine Research Centre, Chang Gung University. 6. Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital. 7. Department of Medicine, Chang Gung University, Taoyuan, Taiwan.
Abstract
Objective: The aim was to estimate familial relative risk (RR) for RA and other autoimmune diseases and the genetic contribution to RA phenotypic variance (heritability). Methods: This study used the Taiwan National Health Insurance Research Database to identify all National Health Insurance registered beneficiaries (n = 23 658 577) in 2010; among them, 37 482 individuals had RA. We estimated familial RRs and 95% CIs of RA and other autoimmune diseases using marginal Cox proportional models and heritability of RA using a threshold liability model. Results: The RR (95% CI) for RA was 328.27 (135.95, 795.63) for twins of RA patients; 11.97 (8.68, 16.52) for siblings; 4.86 (4.16, 5.67) for parents; 4.65 (3.92, 5.50) for offspring; and 2.32 (1.83, 2.95) for spouses. Using a threshold liability model, we estimated that familial transmission was 59.4% (95% CI: 50.3, 69.5%) and that heritability was 43.5% (33.9, 54.1%). The RR (95% CI) in individuals with a first-degree relative with RA was 2.91 (2.49, 3.42) for SLE; 2.92 (1.62, 5.25) for SSc; 3.13 (2.50, 3.93) for primary SS; 0.95 (0.36, 2.51) for idiopathic inflammatory myositis; 1.96 (1.54, 2.48) for type 1 diabetes mellitus; 3.32 (1.82, 5.95) for multiple sclerosis; 1.31 (1.31, 2.43) for IBD; 2.76 (2.46, 3.10) for AS; and 1.65 (1.54, 1.77) for psoriasis. Conclusion: The risks of RA and other autoimmune diseases increased in individuals with an RA family history. Approximately two-thirds of RA phenotypic variation is explained by familial factors.
Objective: The aim was to estimate familial relative risk (RR) for RA and other autoimmune diseases and the genetic contribution to RA phenotypic variance (heritability). Methods: This study used the Taiwan National Health Insurance Research Database to identify all National Health Insurance registered beneficiaries (n = 23 658 577) in 2010; among them, 37 482 individuals had RA. We estimated familial RRs and 95% CIs of RA and other autoimmune diseases using marginal Cox proportional models and heritability of RA using a threshold liability model. Results: The RR (95% CI) for RA was 328.27 (135.95, 795.63) for twins of RA patients; 11.97 (8.68, 16.52) for siblings; 4.86 (4.16, 5.67) for parents; 4.65 (3.92, 5.50) for offspring; and 2.32 (1.83, 2.95) for spouses. Using a threshold liability model, we estimated that familial transmission was 59.4% (95% CI: 50.3, 69.5%) and that heritability was 43.5% (33.9, 54.1%). The RR (95% CI) in individuals with a first-degree relative with RA was 2.91 (2.49, 3.42) for SLE; 2.92 (1.62, 5.25) for SSc; 3.13 (2.50, 3.93) for primary SS; 0.95 (0.36, 2.51) for idiopathic inflammatory myositis; 1.96 (1.54, 2.48) for type 1 diabetes mellitus; 3.32 (1.82, 5.95) for multiple sclerosis; 1.31 (1.31, 2.43) for IBD; 2.76 (2.46, 3.10) for AS; and 1.65 (1.54, 1.77) for psoriasis. Conclusion: The risks of RA and other autoimmune diseases increased in individuals with an RA family history. Approximately two-thirds of RA phenotypic variation is explained by familial factors.
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