Skip to main content

Research Repository

Advanced Search

Familial Aggregation of Systemic Lupus Erythematosus and Coaggregation of Autoimmune Diseases in Affected Families

Kuo, Chang-Fu; Grainge, Matthew J.; Valdes, Ana M.; See, Lai-Chu; Luo, Shue-Fen; Yu, Kuang-Hui; Zhang, Weiya; Doherty, Michael


Chang-Fu Kuo

Profile Image

Professor of Molecular & Genetic Epidemiology

Lai-Chu See

Shue-Fen Luo

Kuang-Hui Yu

Michael Doherty


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.


Kuo, C., Grainge, M. J., Valdes, A. M., See, L., Luo, S., Yu, K., …Doherty, M. (2015). Familial Aggregation of Systemic Lupus Erythematosus and Coaggregation of Autoimmune Diseases in Affected Families. JAMA Internal Medicine, 175(9), 1518-1526.

Journal Article Type Article
Acceptance Date Jun 2, 2015
Online Publication Date Jul 20, 2015
Publication Date Sep 1, 2015
Deposit Date Aug 22, 2017
Journal JAMA Internal Medicine
Print ISSN 2168-6106
Electronic ISSN 2168-6114
Publisher American Medical Association
Peer Reviewed Peer Reviewed
Volume 175
Issue 9
Pages 1518-1526
Keywords Adolescent, Adult, Cluster Analysis, Cohort Studies, FemaleGenetic Predisposition to Disease, Humans,Lupus Erythematosus, Systemic/*epidemiology/genetics, MaleMiddle Aged, Prevalence, Taiwan/epidemiology, Young Adult
Public URL
Publisher URL
Copyright Statement Copyright information regarding this work can be found at the following address: