Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families

Kuo, Chang-Fu and Grainge, Matthew J. and Valdes, Ana M. and See, Lai-Chu and Luo, Shue-Fen and Yu, Kuang-Hui and Zhang, Weiya and Doherty, Michael (2015) Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families. JAMA Internal Medicine, 175 (9). pp. 1518-1526. ISSN 2168-6114

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Abstract

IMPORTANCE: 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.

DESIGN, SETTING, AND PARTICIPANTS: 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.

MAIN OUTCOMES AND MEASURES: 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 Sjogren 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 AND RELEVANCE: 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.

Item Type: Article
Keywords: Adolescent, Adult, Cluster Analysis, Cohort Studies, Female Genetic Predisposition to Disease, Humans, Lupus Erythematosus, Systemic/*epidemiology/genetics, Male Middle Aged, Prevalence, Taiwan/epidemiology, Young Adult
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Epidemiology and Public Health
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Rheumatology, Orthopaedics and Dermatology
Identification Number: 10.1001/jamainternmed.2015.3528
Depositing User: Claringburn, Tara
Date Deposited: 22 Aug 2017 10:11
Last Modified: 22 Sep 2017 19:26
URI: http://eprints.nottingham.ac.uk/id/eprint/45046

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