1. Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.
- Author
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Li, Yun R, Li, Jin, Zhao, Sihai D, Bradfield, Jonathan P, Mentch, Frank D, Maggadottir, S Melkorka, Hou, Cuiping, Abrams, Debra J, Chang, Diana, Gao, Feng, Guo, Yiran, Wei, Zhi, Connolly, John J, Cardinale, Christopher J, Bakay, Marina, Glessner, Joseph T, Li, Dong, Kao, Charlly, Thomas, Kelly A, and Qiu, Haijun
- Subjects
GENETICS of autoimmune diseases ,META-analysis ,SINGLE nucleotide polymorphisms ,MICRORNA ,DEOXYRIBONUCLEASES ,T helper cells ,IMMUNOREGULATION ,CHILDREN'S health - 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 (TH 1, TH 2 and TH 17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases. [ABSTRACT FROM AUTHOR]- Published
- 2015
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