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Genetic sharing and heritability of paediatric age of onset autoimmune diseases

Author

Listed:
  • Yun R. Li

    (Center for Applied Genomics, Children’s Hospital of Philadelphia
    Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania)

  • Sihai D. Zhao

    (University of Illinois at Urbana-Champaign)

  • Jin Li

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Jonathan P. Bradfield

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Maede Mohebnasab

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Laura Steel

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Julie Kobie

    (Perelman School of Medicine, University of Pennsylvania)

  • Debra J. Abrams

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Frank D. Mentch

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Joseph T. Glessner

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Yiran Guo

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Zhi Wei

    (Center for Applied Genomics, Children’s Hospital of Philadelphia
    New Jersey Institute of Technology)

  • John J. Connolly

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Christopher J. Cardinale

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Marina Bakay

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Dong Li

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • S. Melkorka Maggadottir

    (Center for Applied Genomics, Children’s Hospital of Philadelphia
    Children’s Hospital of Philadelphia)

  • Kelly A. Thomas

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Haijun Qui

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Rosetta M. Chiavacci

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Cecilia E. Kim

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Fengxiang Wang

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • James Snyder

    (Center for Applied Genomics, Children’s Hospital of Philadelphia)

  • Berit Flatø

    (Oslo University Hospital)

  • Øystein Førre

    (Oslo University Hospital)

  • Lee A. Denson

    (Center for Inflammatory Bowel Disease, Cincinnati Children's Hospital Medical Center)

  • Susan D. Thompson

    (Divison of Rheumatology, Cincinnati Children’s Hospital Medical Center)

  • Mara L. Becker

    (Toxicology, and Therapeutic Innovation, Children’s Mercy-Kansas City)

  • Stephen L. Guthery

    (University of Utah School of Medicine and Primary Children's Medical Center)

  • Anna Latiano

    (RCCS ‘Casa Sollievo della Sofferenza’)

  • Elena Perez

    (University of Miami Miller School of Medicine)

  • Elena Resnick

    (Institute of Immunology, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital)

  • Caterina Strisciuglio

    (Section of Pediatrics, University of Naples "Federico II")

  • Annamaria Staiano

    (Section of Pediatrics, University of Naples "Federico II")

  • Erasmo Miele

    (Section of Pediatrics, University of Naples "Federico II")

  • Mark S. Silverberg

    (IBD Centre, Mount Sinai Hospital, University of Toronto)

  • Benedicte A. Lie

    (Oslo University Hospital)

  • Marilynn Punaro

    (Texas Scottish Rite Hospital for Children)

  • Richard K. Russell

    (Yorkhill Hospital for Sick Children)

  • David C. Wilson

    (Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh and Child Life and Health, University of Edinburgh)

  • Marla C. Dubinsky

    (Cedars Sinai Medical Center)

  • Dimitri S. Monos

    (Children’s Hospital of Philadelphia
    The Perelman School of Medicine, University of Pennsylvania)

  • Vito Annese

    (Unit of Gastroenterology, Careggi University Hospital)

  • Jane E. Munro

    (Paediatric Rheumatology Unit, Royal Children’s Hospital
    Arthritis and Rheumatology Research, Murdoch Childrens Research Institute)

  • Carol Wise

    (Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children)

  • Helen Chapel

    (University of Oxford)

  • Charlotte Cunningham-Rundles

    (Institute of Immunology, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital)

  • Jordan S. Orange

    (Section of Immunology, Allergy, and Rheumatology, Texas Children’s Hospital)

  • Edward M. Behrens

    (The Perelman School of Medicine, University of Pennsylvania
    Children’s Hospital of Philadelphia)

  • Kathleen E. Sullivan

    (Children’s Hospital of Philadelphia
    The Perelman School of Medicine, University of Pennsylvania)

  • Subra Kugathasan

    (Emory University School of Medicine and Children’s Health Care of Atlanta)

  • Anne M. Griffiths

    (Hospital for Sick Children, University of Toronto)

  • Jack Satsangi

    (Gastrointestinal Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital)

  • Struan F. A. Grant

    (Center for Applied Genomics, Children’s Hospital of Philadelphia
    The Perelman School of Medicine, University of Pennsylvania)

  • Patrick M. A. Sleiman

    (Center for Applied Genomics, Children’s Hospital of Philadelphia
    The Perelman School of Medicine, University of Pennsylvania)

  • Terri H. Finkel

    (Nemours Children’s Hospital)

  • Constantin Polychronakos

    (McGill University)

  • Robert N. Baldassano

    (The Perelman School of Medicine, University of Pennsylvania
    Children’s Hospital of Philadelphia)

  • Eline T. Luning Prak

    (Perelman School of Medicine University of Pennsylvania)

  • Justine A. Ellis

    (Genes, Environment and Complex Disease, Murdoch Childrens Research Institute
    University of Melbourne)

  • Hongzhe Li

    (Perelman School of Medicine, University of Pennsylvania)

  • Brendan J. Keating

    (Center for Applied Genomics, Children’s Hospital of Philadelphia
    The Perelman School of Medicine, University of Pennsylvania)

  • Hakon Hakonarson

    (Center for Applied Genomics, Children’s Hospital of Philadelphia
    The Perelman School of Medicine, University of Pennsylvania
    Children’s Hospital of Philadelphia)

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-h2). SNP-h2 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-h2 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.

Suggested Citation

  • Yun R. Li & Sihai D. Zhao & Jin Li & Jonathan P. Bradfield & Maede Mohebnasab & Laura Steel & Julie Kobie & Debra J. Abrams & Frank D. Mentch & Joseph T. Glessner & Yiran Guo & Zhi Wei & John J. Conno, 2015. "Genetic sharing and heritability of paediatric age of onset autoimmune diseases," Nature Communications, Nature, vol. 6(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9442
    DOI: 10.1038/ncomms9442
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