Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families
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 environme...
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American Medical Association
2015
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| Online Access: | https://eprints.nottingham.ac.uk/45046/ |
| _version_ | 1848797056352649216 |
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| author | Kuo, Chang-Fu Grainge, Matthew J. Valdes, Ana M. See, Lai-Chu Luo, Shue-Fen Yu, Kuang-Hui Zhang, Weiya Doherty, Michael |
| author_facet | Kuo, Chang-Fu Grainge, Matthew J. Valdes, Ana M. See, Lai-Chu Luo, Shue-Fen Yu, Kuang-Hui Zhang, Weiya Doherty, Michael |
| author_sort | Kuo, Chang-Fu |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:57:48Z |
| format | Article |
| id | nottingham-45046 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:57:48Z |
| publishDate | 2015 |
| publisher | American Medical Association |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-450462020-05-04T17:12:39Z https://eprints.nottingham.ac.uk/45046/ 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 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. American Medical Association 2015-07-20 Article PeerReviewed Kuo, Chang-Fu, Grainge, Matthew J., Valdes, Ana M., See, Lai-Chu, Luo, Shue-Fen, Yu, Kuang-Hui, 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 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 doi:10.1001/jamainternmed.2015.3528 doi:10.1001/jamainternmed.2015.3528 |
| spellingShingle | 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 Kuo, Chang-Fu Grainge, Matthew J. Valdes, Ana M. See, Lai-Chu Luo, Shue-Fen Yu, Kuang-Hui Zhang, Weiya Doherty, Michael Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families |
| title | Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families |
| title_full | Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families |
| title_fullStr | Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families |
| title_full_unstemmed | Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families |
| title_short | Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families |
| title_sort | familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families |
| topic | 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 |
| url | https://eprints.nottingham.ac.uk/45046/ https://eprints.nottingham.ac.uk/45046/ |