title: Familial Aggregation of Systemic Lupus Erythematosus and Coaggregation of Autoimmune Diseases in Affected Families.
abstract: OBJECTIVE
  Relatives of patients with systemic lupus erythematosus (SLE) appear to be at higher risk of SLE and other autoimmune diseases, but estimates of individual familial risks are largely unavailable or unreliable. Furthermore, relative contributions of genetic, shared, and unshared environmental factors to SLE susceptibility remain unclear.
  
  
  OBJECTIVE
  To examine familial aggregation and heritability of SLE and the relative risks (RRs) of other autoimmune diseases in relatives of patients with SLE.
  
  
  METHODS
  A population-based family study using the Taiwan National Health Insurance Research Database was conducted. Participants included all individuals (N = 23,658,577) registered with that database in 2010; of these, 18,283 had SLE. We identified 21,009,551 parent-child relationships, 17,168,340 full sibling pairs, and 342,066 twin pairs. Diagnoses of SLE were ascertained from March 1, 1995, to December 31, 2010, and analysis was conducted between March 1 and August 15, 2014.
  
  
  METHODS
  The prevalence and RRs of SLE and other autoimmune diseases in relatives and spouses of patients with SLE as well as the relative contributions of heritability, shared, and nonshared environmental factors to SLE susceptibility.
  
  
  RESULTS
  Among the more than 23 million participants, the RRs (95% CIs) for SLE were 315.94 (210.66-473.82) for twins of the patients, 23.68 (20.13-27.84) for siblings, 11.44 (9.74-13.43) for parents, 14.42 (12.45-16.70) for offspring, and 4.44 (2.38-8.30) for spouses without genetic similarity. The accountability for phenotypic variance of SLE was 43.9% for heritability, 25.8% for shared environmental factors, and 30.3% for nonshared environmental factors. The RRs (95% CIs) in individuals with a first-degree relative with SLE were 5.87 (4.89-7.05) for primary Sjögren syndrome, 5.40 (3.37-8.65) for systemic sclerosis, 2.95 (2.04-4.26) for myasthenia gravis, 2.77 (1.45-5.32) for idiopathic inflammatory myositis, 2.66 (2.28-3.11) for rheumatoid arthritis, 2.58 (1.16-5.72) for multiple sclerosis, 1.68 (1.22-2.32) for type 1 diabetes mellitus, 1.39 (0.66-2.91) for inflammatory bowel diseases, and 0.86 (0.43-1.71) for vasculitis.
  
  
  CONCLUSIONS
  The individual risks of SLE and other autoimmune diseases were increased in families that included patients with SLE. The heritability of SLE was estimated to be 43.9%. These data should be considered when counseling families with affected members.
authors.affiliation: Division of Rheumatology, Orthopaedics, and Dermatology, School of Medicine, University of Nottingham, Nottingham, England2Division of Rheumatology, Allergy, and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Chang-Fu
authors.initials: CF
authors.lastname: Kuo
authors.affiliation: Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, England.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Grainge
authors.affiliation: Division of Rheumatology, Orthopaedics, and Dermatology, School of Medicine, University of Nottingham, Nottingham, England.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.affiliation: Department of Public Health, College of Medicine and Biostatistics Core Laboratory, Molecular Medicine Research Centre, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Lai-Chu
authors.initials: LC
authors.lastname: See
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Shue-Fen
authors.initials: SF
authors.lastname: Luo
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Kuang-Hui
authors.initials: KH
authors.lastname: Yu
authors.affiliation: Division of Rheumatology, Orthopaedics, and Dermatology, School of Medicine, University of Nottingham, Nottingham, England.
authors.forename: Weiya
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Rheumatology, Orthopaedics, and Dermatology, School of Medicine, University of Nottingham, Nottingham, England.
authors.forename: Michael
authors.initials: M
authors.lastname: Doherty
mesh_terms: D000293:Adolescent; D000328:Adult; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult