Familial aggregation of rheumatoid arthritis and co-aggregation of autoimmune diseases in affected families: a nationwide population-based study.
The aim was to estimate familial relative risk (RR) for RA and other autoimmune diseases and the genetic contribution to RA phenotypic variance (heritability).



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.



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.



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.
Academic Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK.|Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Chang-Fu
CF
Kuo
Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.
Matthew J
MJ
Grainge
Academic Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK.
Ana M
AM
Valdes
Department of Public Health, College of Medicine.|Biostatistics Core Laboratory, Molecular Medicine Research Centre, Chang Gung University.
Lai-Chu
LC
See
Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Kuang-Hui
KH
Yu
Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital.|Department of Medicine, Chang Gung University, Taoyuan, Taiwan.
S W Steven
SWS
Shaw
Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Department of Medicine, Chang Gung University, Taoyuan, Taiwan.
Shue-Fen
SF
Luo
Academic Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK.
Weiya
W
Zhang
Academic Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK.
Michael
M
Doherty
D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012042:Registries; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
familial aggregation; familial transmission; genetic epidemiology; heritability; rheumatoid arthritis