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Nat Commun. 2015 Oct 9;6:8442. doi: 10.1038/ncomms9442.

Genetic sharing and heritability of paediatric age of onset autoimmune diseases.

Author information

1
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
2
Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
3
Department of Statistics, University of Illinois at Urbana-Champaign, Champaign, Illinois 61820, USA.
4
Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
5
Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey 07103, USA.
6
Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
7
Department of Rheumatology, Oslo University Hospital, Rikshospitalet, Oslo 0372, Norway.
8
Center for Inflammatory Bowel Disease, Division of Gastroenterology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
9
Divison of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
10
Division of Rheumatology and Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation, Children's Mercy-Kansas City, Kansas City, Missouri 64108, USA.
11
Department of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, Utah 84113, USA.
12
RCCS 'Casa Sollievo della Sofferenza', Division of Gastroenterology, San Giovanni Rotondo 71013, Italy.
13
Division of Pediatric Allergy and Immunology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
14
Institute of Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, New York 10029, USA.
15
Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples 80138, Italy.
16
IBD Centre, Mount Sinai Hospital, University of Toronto, 441-600 University Avenue, Toronto, Ontario, Canada M5G 1X5.
17
Department of Immunology, Oslo University Hospital, Rikshospitalet, 0027 Oslo 0372, Norway.
18
Texas Scottish Rite Hospital for Children, Dallas, Texas 750219, USA.
19
Yorkhill Hospital for Sick Children, Glasgow G38SJ, Scotland.
20
Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh and Child Life and Health, University of Edinburgh, Edinburgh EH9 1UW, UK.
21
Departments of Pediatrics and Common Disease Genetics, Cedars Sinai Medical Center, Los Angeles, California 90048, USA.
22
Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
23
Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
24
Unit of Gastroenterology, Department of Medical and Surgical Specialties, Careggi University Hospital, Viale Pieraccini 18, Florence 50139, Italy.
25
Paediatric Rheumatology Unit, Royal Children's Hospital, Parkville, Victoria 3052, Australia.
26
Arthritis and Rheumatology Research, Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia.
27
Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children, Dallas, Texas 750219, USA.
28
Department of Clinical Immunology, Nuffield Department of Medicine, University of Oxford, OX1 1NF, UK.
29
Section of Immunology, Allergy, and Rheumatology, Department of Pediatric Medicine, Texas Children's Hospital, Houston, Texas 77030, USA.
30
Division of Rheumatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
31
Department of Pediatrics, Emory University School of Medicine and Children's Health Care of Atlanta, Atlanta, Georgia 30329, USA.
32
Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.
33
Gastrointestinal Unit, Division of Medical Sciences, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
34
Department of Pediatrics, Nemours Children's Hospital, Orlando, Florida 32827, USA.
35
Departments of Pediatrics and Human Genetics, McGill University, Montreal, Quebec, Canada H3H 1P3.
36
Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
37
Department of Pathology and Lab Medicine, Perelman School of Medicine University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
38
Genes, Environment and Complex Disease, Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia.
39
Department of Paediatrics, University of Melbourne, Parkville, Victoria 3052, Australia.
40
Division of Pulmonary Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.

Abstract

Autoimmune diseases (AIDs) are polygenic diseases affecting 7-10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP-h(2)). SNP-h(2) estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP-h(2) in T1D and JIA, but does not significantly contribute to the pairwise rG. Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations between autoimmune diseases previously reported in adult cohorts.

PMID:
26450413
PMCID:
PMC4633631
DOI:
10.1038/ncomms9442
[Indexed for MEDLINE]
Free PMC Article

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