Journal article

Genetic sharing and heritability of paediatric age of onset autoimmune diseases

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 Connolly, Christopher J Cardinale, Marina Bakay, Dong Li, S Melkorka Maggadottir, Kelly A Thomas, Haijun Qui, Rosetta M Chiavacci Show all

Nature Communications | NATURE PUBLISHING GROUP | Published : 2015

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..

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Grants

Awarded by NIH F30 Individual NRSA Training Grant



Awarded by NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES


Awarded by NATIONAL HUMAN GENOME RESEARCH INSTITUTE


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Awarded by Medical Research Council


Awarded by Medical Research Foundation


Awarded by Crohn"s and Colitis UK


Awarded by Chief Scientist Office


Funding Acknowledgements

We thank the patients and their families for their participation in the genotyping studies and in the Biobank Repository at the Center for Applied Genomics. We are also thankful for the contributions of the Italian IBD Group, including Cucchiara S (Roma), Lionetti P (Firenze), Barabino G (Genova), de Angelis GL (Parma), Guariso G (Padova), Catassi C (Ancona), Lombardi G (Pescara), Staiano AM (Napoli), De Venuto D (Bari), Romano C (Messina), D'inca R (Padova), Vecchi M (Milano), Andriulli A and Bossa F (S. Giovanni Rotondo). Y.R.L. is supported by the Paul and Daisy Soros Fellowship for New Americans and an NIH F30 Individual NRSA Training Grant (1F30AR066486). This study was supported by Institutional Development Funds from the Children's Hospital of Philadelphia, and by DP3DK085708, RC1AR058606, U01HG006830, the Crohn's and Colitis Foundation, the Juvenile Diabetes Research Foundation and a grant from the LRI to E.L.P.