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Arthritis & Rheumatology DOI 10.1002/art.39129
Sibling exposure and risk of juvenile idiopathic arthritis in the ChiLdhood Arthritis Risk factor Identification sTudY (CLARITY)
Jessica Miller1, Anne-Louise Ponsonby2,3, Angela Pezic2, Andrew Kemp2, Susan E Piper4, Jonathan D Akikusa5,6, Roger C Allen5,6, Jane E Munro5,6, Justine A Ellis1,3*
1
Genes, Environment & Complex Disease, Murdoch Childrens Research Institute, Parkville,
Victoria 3052 Australia 2
Environmental & Genetic Epidemiology Research, Murdoch Childrens Research Institute,
Parkville, Victoria 3052 Australia 3
Department of Paediatrics, University of Melbourne, Victoria 3010 Australia
4
Paediatric Rheumatology Department, Monash Children’s Hospital, Monash Medical
Centre, Clayton Victoria 3168 Australia 5
Arthritis & Rheumatology Research, Murdoch Childrens Research Institute, Parkville,
Victoria 3052 Australia 6
Paediatric Rheumatology Unit, Royal Children’s Hospital, Parkville, Victoria 3052
Australia
*
Address for Correspondence: Dr Justine A Ellis, Genes, Environment & Complex Disease,
Murdoch Childrens Research Institute, 50 Flemington Road, Parkville, Victoria 3052 Australia. T: +61 3 8341 6311. E: [email protected].
Keywords: Juvenile idiopathic arthritis, hygiene hypothesis, sibling exposure, environment, disease risk
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/art.39129 © 2015 American College of Rheumatology Received: Aug 08, 2014; Revised: Feb 25, 2015; Accepted: Mar 19, 2015 This article is protected by copyright. All rights reserved.
Arthritis & Rheumatology
Page 2 of 41
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, but the hypothesis has not been tested in detail. Method: We therefore conducted a comprehensive analysis of the role of sibling exposure in JIA risk within the CLARITY JIA case - hospital control sample (302 cases, 676 controls) from Victoria, Australia. Results: We found that, compared to being an only child, having any siblings was protective of JIA (adjusted OR=0.46, 95% CI 0.28 - 0.74, p=0.001). The protective association appeared to increase with increasing number of siblings (e.g. ≥3 siblings, AOR=0.25, 95% CI 0.13 0.48, p
Arthritis & Rheumatology DOI 10.1002/art.39129
Sibling exposure and risk of juvenile idiopathic arthritis in the ChiLdhood Arthritis Risk factor Identification sTudY (CLARITY)
Jessica Miller1, Anne-Louise Ponsonby2,3, Angela Pezic2, Andrew Kemp2, Susan E Piper4, Jonathan D Akikusa5,6, Roger C Allen5,6, Jane E Munro5,6, Justine A Ellis1,3*
1
Genes, Environment & Complex Disease, Murdoch Childrens Research Institute, Parkville,
Victoria 3052 Australia 2
Environmental & Genetic Epidemiology Research, Murdoch Childrens Research Institute,
Parkville, Victoria 3052 Australia 3
Department of Paediatrics, University of Melbourne, Victoria 3010 Australia
4
Paediatric Rheumatology Department, Monash Children’s Hospital, Monash Medical
Centre, Clayton Victoria 3168 Australia 5
Arthritis & Rheumatology Research, Murdoch Childrens Research Institute, Parkville,
Victoria 3052 Australia 6
Paediatric Rheumatology Unit, Royal Children’s Hospital, Parkville, Victoria 3052
Australia
*
Address for Correspondence: Dr Justine A Ellis, Genes, Environment & Complex Disease,
Murdoch Childrens Research Institute, 50 Flemington Road, Parkville, Victoria 3052 Australia. T: +61 3 8341 6311. E: [email protected].
Keywords: Juvenile idiopathic arthritis, hygiene hypothesis, sibling exposure, environment, disease risk
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/art.39129 © 2015 American College of Rheumatology Received: Aug 08, 2014; Revised: Feb 25, 2015; Accepted: Mar 19, 2015 This article is protected by copyright. All rights reserved.
Arthritis & Rheumatology
Page 2 of 41
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, but the hypothesis has not been tested in detail. Method: We therefore conducted a comprehensive analysis of the role of sibling exposure in JIA risk within the CLARITY JIA case - hospital control sample (302 cases, 676 controls) from Victoria, Australia. Results: We found that, compared to being an only child, having any siblings was protective of JIA (adjusted OR=0.46, 95% CI 0.28 - 0.74, p=0.001). The protective association appeared to increase with increasing number of siblings (e.g. ≥3 siblings, AOR=0.25, 95% CI 0.13 0.48, p
