| Literature DB >> 26301688 |
Yun R Li1,2, Jin Li1, Sihai D Zhao3, Jonathan P Bradfield1, Frank D Mentch1, S Melkorka Maggadottir1,4, Cuiping Hou1, Debra J Abrams1, Diana Chang5,6, Feng Gao5, Yiran Guo1, Zhi Wei7, John J Connolly1, Christopher J Cardinale1, Marina Bakay1, Joseph T Glessner1, Dong Li1, Charlly Kao1, Kelly A Thomas1, Haijun Qiu1, Rosetta M Chiavacci1, Cecilia E Kim1, Fengxiang Wang1, James Snyder1, Marylyn D Richie8, Berit Flatø9, Øystein Førre9, Lee A Denson10, Susan D Thompson11, Mara L Becker12, Stephen L Guthery13, Anna Latiano14, Elena Perez15, Elena Resnick16, Richard K Russell17, David C Wilson18, Mark S Silverberg19, Vito Annese20, Benedicte A Lie21, Marilynn Punaro22, Marla C Dubinsky23, Dimitri S Monos24,25, Caterina Strisciuglio26, Annamaria Staiano26, Erasmo Miele26, Subra Kugathasan27, Justine A Ellis28,29, Jane E Munro30,31, Kathleen E Sullivan4,25, Carol A Wise32, Helen Chapel33, Charlotte Cunningham-Rundles16, Struan F A Grant1,25, Jordan S Orange34, Patrick M A Sleiman1,25, Edward M Behrens25,35, Anne M Griffiths36, Jack Satsangi37, Terri H Finkel38, Alon Keinan5,6, Eline T Luning Prak39, Constantin Polychronakos40, Robert N Baldassano25,41, Hongzhe Li39, Brendan J Keating1,25, Hakon Hakonarson1,25,42.
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 polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases.Entities:
Mesh：
Year: 2015 PMID： 26301688 PMCID： PMC4863040 DOI： 10.1038/nm.3933
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 87.241