Journal article
Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases
Yun R Li, Jin Li, Sihai D Zhao, Jonathan P Bradfield, Frank D Mentch, S Melkorka Maggadottir, Cuiping Hou, Debra J Abrams, Diana Chang, Feng Gao, Yiran Guo, Zhi Wei, John J Connolly, Christopher J Cardinale, Marina Bakay, Joseph T Glessner, Dong Li, Charlly Kao, Kelly A Thomas, Haijun Qiu Show all
Nature Medicine | NATURE PUBLISHING GROUP | Published : 2015
DOI: 10.1038/nm.3933
Abstract
Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphis..
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Awarded by Wellcome Trust
Awarded by NIH
Awarded by Medical Research Council
Awarded by Medical Research Foundation
Awarded by Chief Scientist Office
Awarded by Crohn"s and Colitis UK
Awarded by NATIONAL CANCER INSTITUTE
Awarded by NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
Awarded by NATIONAL CENTER FOR RESEARCH RESOURCES
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
Funding Acknowledgements
We thank the subjects and their families for their participation in genotyping studies and the Biobank Repository at the Center for Applied Genomics at the Children's Hospital of Philadelphia. We acknowledge M.V. Holmes, H. Matsunami, L. Steel and E. Carrigan for their technical assistance and review of the manuscript. We are also thankful for the contributions of the Italian IBD Group, including S. Cucchiara (Roma), P. Lionetti (Firenze), G. Barabino (Genova), G. L. de Angelis (Parma), G. Guariso (Padova), C. Catassi (Ancona), G. Lombardi (Pescara), A.M. Staiano (Napoli), D. De Venuto (Bari), C. Romano (Messina), R. D'inca (Padova), M. Vecchi (Milano), A. Andriulli and F. Bossa (S. Giovanni Rotondo). The data sets used for the replication analyses were obtained through dbGaP accession numbers phs000344, phs000127, phs000274, phs000171, phs000224, phs000130, phs000019, phs000091, phs000206, phs000168, phs000138, phs000125 and phs000092. We thank the NIH data repository, the investigators who contributed the phenotype data and DNA samples from their original studies, and the primary funding organizations that supported these contributing investigators. This study made use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113. Y.R.L. is supported by the Paul and Daisy Soros Fellowship for New Americans and the NIH F30 Individual NRSA Training Grant. This study was supported by Institutional Development Funds from The Children's Hospital of Philadelphia and by DP3DK085708, RC1AR058606, U01HG006830, the Crohn's & Colitis Foundation of America, the Juvenile Diabetes Research Foundation, NIH grant CA127334 (to H. L. and S.D.Z.), the UK National Institutes of Healthcare Research (to H. C.) and a grant from the Lupus Research Institute (to E.T.L.P.). This work was supported in part by the NIH (grant R01-HG006849 to A.K.). F.G. is a Howard Hughes Medical Institute International Student Research fellow.