title: Sibling Exposure and Risk of Juvenile Idiopathic Arthritis.
abstract: OBJECTIVE
  Susceptibility to juvenile idiopathic arthritis (JIA) is presumed to be determined by both genes and environment. However, the environmental factors remain largely unknown. The hygiene hypothesis suggests that exposure to siblings, as a marker of exposure to microbes in early life, may protect against the development of later immune disorders. Some prior evidence suggests this may also be true for JIA. The present study was undertaken to test this hypothesis in detail.
  
  
  METHODS
  We conducted a comprehensive analysis of the role of sibling exposure in JIA risk within the Childhood Arthritis Risk Factor Identification Study JIA case-hospital control sample (302 cases and 676 controls) from Victoria, Australia.
  
  
  RESULTS
  We found that, compared to being an only child, having any siblings was protective against JIA, with an adjusted odds ratio (OR) of 0.46 (95% confidence interval [95% CI] 0.28-0.74) (P = 0.001). The protective association appeared to increase with increasing number of siblings (e.g., for ≥3 siblings, adjusted OR 0.25 [95% CI 0.13-0.48], P < 0.001). A protective association of siblings was also observed when we considered cumulative sibling years by age 6 (e.g., for ≥3 years of exposure versus no exposure, adjusted OR 0.49 [95% CI 0.30-0.79], P = 0.003). We also compared cases to a second control sample (n = 341) collected from the community and weighted to represent the child population of Victoria. Data remained supportive of an association between sibling exposure and protection against JIA, particularly for exposure to younger siblings.
  
  
  CONCLUSIONS
  Increased exposure to siblings is associated with a reduced risk of disease in our sample. This suggests that increased microbial exposure in childhood may confer protection against the development of JIA.
authors: Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors: Jessica
authors: J
authors: Miller
authors: Murdoch Childrens Research Institute, Parkville, Victoria, Australia, and University of Melbourne, Melbourne, Victoria, Australia.
authors: Anne-Louise
authors: AL
authors: Ponsonby
authors: Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors: Angela
authors: A
authors: Pezic
authors: Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors: Andrew
authors: A
authors: Kemp
authors: Monash Children's Hospital, Monash Medical Centre, Clayton, Victoria, Australia.
authors: Susan E
authors: SE
authors: Piper
authors: Murdoch Childrens Research Institute and Royal Children's Hospital, Parkville, Victoria, Australia.
authors: Jonathan D
authors: JD
authors: Akikusa
authors: Murdoch Childrens Research Institute and Royal Children's Hospital, Parkville, Victoria, Australia.
authors: Roger C
authors: RC
authors: Allen
authors: Murdoch Childrens Research Institute and Royal Children's Hospital, Parkville, Victoria, Australia.
authors: Jane E
authors: JE
authors: Munro
authors: Murdoch Childrens Research Institute, Parkville, Victoria, Australia, and University of Melbourne, Melbourne, Victoria, Australia.
authors: Justine A
authors: JA
authors: Ellis
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001171:Arthritis, Juvenile / Q000453:epidemiology* / Q000517:prevention & control*; D001315:Australia; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004781:Environmental Exposure; D005191:Family Characteristics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D065840:Protective Factors; D012307:Risk Factors; D035781:Siblings