title: Quantification of the familial contribution to juvenile idiopathic arthritis.
abstract: 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 approximately 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 approximately 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 x 10(-8)). The RR of JIA in first cousins was also increased (5.82, 95% CI 2.5-13.8, P < 6.07 x 10(-5)).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pediatric Rheumatology, Emory University School of Medicine, 2015 Uppergate Drive NE, Atlanta, GA 30322, USA. sprahal@emory.edu
authors.forename: Sampath
authors.initials: S
authors.lastname: Prahalad
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Zeft
authors.forename: Richard
authors.initials: R
authors.lastname: Pimentel
authors.forename: Bronte
authors.initials: B
authors.lastname: Clifford
authors.forename: Bernadette
authors.initials: B
authors.lastname: McNally
authors.forename: Geraldine P
authors.initials: GP
authors.lastname: Mineau
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Jorde
authors.forename: John F
authors.initials: JF
authors.lastname: Bohnsack
mesh_terms: D001171:Arthritis, Juvenile / Q000235:genetics*; D016022:Case-Control Studies; D016208:Databases, Factual; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D008297:Male; D010375:Pedigree; D012306:Risk; D012307:Risk Factors; D014589:Utah