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Study Examines Shared Genetic Architecture in Ten Pediatric Autoimmune Diseases
Using genome-wide association studies (GWASs), researchers have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases.
A team of researchers recently conducted an inverse χ2 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.
The research team included 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, Rosetta M Chiavacci, Cecilia E Kim, Fengxiang Wang, James Snyder, and Marylyn D Richie.
The are variously affiliated with The Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; the Department of Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; the Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; the Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA; the Program in Computational Biology and Medicine, Cornell University, Ithaca, New York, USA, and the Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey, USA.
For their study, the team 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 team functionally enriched the pAID-associated single-nucleotide polymorphisms (SNPs) for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants.
They 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.
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Jefferson Adams is a freelance writer living in San Francisco. His poems, essays and photographs have appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden's Ferry Review, Huffington Post, the Mississippi Review, and Slate among others.
He is a member of both the National Writers Union, the International Federation of Journalists, and covers San Francisco Health News for Examiner.com.View all articles by Jefferson Adams
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