1. Genetic risk factors for pediatric-onset multiple sclerosis
- Author
-
Tanuja Chitnis, Moses Rodriguez, Emmanuelle Waubant, Ingrid Kockum, Jayne Ness, Lisa F. Barcellos, Jennifer Rubin, Jan M. Tillema, Lauren Krupp, Diana Quach, Stacy J. Caillier, Gregory Aaen, Leslie Benson, Yolanda Harris, T. Charles Casper, Shelly Roalstad, Teri Schreiner, Soe Mar, Tomas Olsson, Jan Hillert, Amy Waldman, Benjamin Greenberg, Milena A. Gianfrancesco, Jennifer Graves, Bianca Weinstock-Guttman, Meghan Candee, Xiaorong Shao, Ling Shen, Anita Belman, Janace Hart, Pernilla Stridh, Timothy Lotze, Brooke Rhead, Ilana Kahn, Mark Gorman, Catherine Schaefer, Lars Alfredsson, John W. Rose, Anna Karin Hedström, and Hong Quach
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Multiple Sclerosis ,Pediatric onset ,Bioinformatics ,Major histocompatibility complex ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Epidemiology ,Humans ,Medicine ,Genetic Predisposition to Disease ,Genetic Testing ,Genetic risk ,Sweden ,biology ,business.industry ,Multiple sclerosis ,Genetic variants ,Odds ratio ,medicine.disease ,Logistic Models ,030104 developmental biology ,Neurology ,Etiology ,biology.protein ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,HLA-DRB1 Chains - Abstract
Background: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. Methods: Cases with onset Results: HLA–DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p −16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated ( p avg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p −16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA–DRB1*15:01 and HLA–A*02. Conclusion: Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA–DRB1*15:01 and HLA–A*02 are also associated with POMS.
- Published
- 2017