Citations 1
miRNAcontributions to pediatric‐onset multiple sclerosis inferred fromGWAS
Rhead, Brooke , Shao, Xiaorong, Lotze, Timothy , Schreiner, Teri , Belman, Anita , Greenberg, Benjamin , Aaen, Gregory , Tillema, Jan Mendelt, Rodriguez, Moses , Hart, Janace, Caillier, Stacy J. , Ness, Jayne , Harris, Yolanda, Rubin, Jennifer , Candee, Meghan , Gorman, Mark , Mar, Soe , Kahn, Ilana , Rose, John , Casper, T. Charles , Quach, Hong , Quach, Diana , Schaefer, Catherine , Barcellos, Lisa F. , Tillema, Jan M, Waubant, Emmanuelle L. , Rodriguez, Moses , Greenberg, Benjamin M , Graves, Jennifer , Chitnis, Tanuja , Waldman, Amy , Schreiner, Teri , Krupp, Lauren , Weinstock‐Guttman, Bianca , Benson, Leslie, Rubin, Jennifer P
Annals of Clinical and Translational Neurology | May 16, 2019 | Volume: 6 | Issue: 6 | Pages: 1053-1061
AbstractObjectiveOnset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatricMS, or ped‐MS). Epigenetic influences are strongly implicated inMSpathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncodingRNAs that affect gene expression by binding target genemRNAs. Few studies have specifically examined miRNAs in ped‐MS, but individuals developingMSat an early age may carry a relatively high burden of genetic risk factors, and miRNAdysregulation may therefore play a larger role in the development of ped‐MSthan in adult‐onsetMS. This study aimed to look for evidence of miRNAinvolvement in ped‐MSpathogenesis.MethodsGWASresults from 486 ped‐MScases and 1362 controls from the U.S. PediatricMSNetwork and Kaiser Permanente Northern California membership were investigated for miRNA‐specific signals. First, enrichment of miRNA‐target gene network signals was evaluated usingMIGWASsoftware. Second,SNPs in miRNAgenes and in target gene binding sites (miR−SNPs) were tested for association with ped‐MS, and pathway analysis was performed on associated target genes.ResultsMIGWASanalysis showed that miRNA‐target gene signals were enriched inGWAS(P = 0.038) and identified 39 candidate biomarker miRNA‐target gene pairs, including immune and neuronal signaling genes. The miR‐SNPanalysis implicated dysregulation of miRNAbinding to target genes in five pathways, mainly involved in immune signaling.InterpretationEvidence fromGWASsuggests that miRNAs play a role in ped‐MSpathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA‐target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility.