Open AccessQuantification of the familial contribution to juvenile idiopathic arthritis
Author(s) -
Prahalad Sampath,
Zeft Andrew S.,
Pimentel Richard,
Clifford Bronte,
McNally Bernadette,
Mineau Geraldine P.,
Jorde Lynn B.,
Bohnsack John F.
Publication year - 2010
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.27516
Subject(s) - proband , medicine , pedigree chart , relative risk , arthritis , family aggregation , population , confidence interval , cohort , juvenile , pediatrics , demography , disease , genetics , biology , mutation , gene , environmental health , sociology
Objective We previously demonstrated that there is familial aggregation of juvenile idiopathic arthritis (JIA). Using a large JIA cohort, we sought to identify additional clusters of JIA cases and to calculate robust estimates of the relative risk (RR) of JIA in the siblings and cousins of JIA probands. We also estimated the population attributable risk (PAR) of familial factors in JIA. Methods A probabilistic record‐linking analysis was performed by matching the records of 862 patients with JIA with the records of ∼7 million individuals in the Utah Population Database (UPDB), a computerized genealogic database. For each patient, 5 control subjects matched for birth year and sex were selected from the UPDB. Specialized software was used to test for familial aggregation of disease, to estimate the magnitude of familial risks, and to identify families at high risk of disease. Results We identified 22 founders who had significantly more descendants with JIA than expected (5–13 descendants; P values ranged from <0.0001 to <0.008). The PAR of familial factors for JIA was ∼13%. The RR of JIA in the siblings of patients was significantly increased (11.6, 95% confidence interval [95% CI] 4.9–27.5, P < 2.59 × 10 −8 ). The RR of JIA in first cousins was also increased (5.82, 95% CI 2.5–13.8, P < 6.07 × 10 −5 ). Conclusion We have identified the largest sets of JIA pedigrees described to date. Approximately 13% of cases of JIA can be attributed to familial factors. Siblings and first cousins of probands with JIA have an increased risk of JIA. The observed decline in the magnitude of risk between siblings and cousins suggests that JIA is influenced by shared genetic factors.