TY - JOUR
T1 - Genetic risk factors for pediatric-onset multiple sclerosis
AU - for the Network of Pediatric Multiple Sclerosis Centers
AU - Gianfrancesco, Milena A.
AU - Stridh, Pernilla
AU - Shao, Xiaorong
AU - Rhead, Brooke
AU - Graves, Jennifer S.
AU - Chitnis, Tanuja
AU - Waldman, Amy
AU - Lotze, Timothy
AU - Schreiner, Teri
AU - Belman, Anita
AU - Greenberg, Benjamin
AU - Weinstock–Guttman, Bianca
AU - Aaen, Gregory
AU - Tillema, Jan M.
AU - Hart, Janace
AU - Caillier, Stacy
AU - Ness, Jayne
AU - Harris, Yolanda
AU - Rubin, Jennifer
AU - Candee, Meghan
AU - Krupp, Lauren
AU - Gorman, Mark
AU - Benson, Leslie
AU - Rodriguez, Moses
AU - Mar, Soe
AU - Kahn, Ilana
AU - Rose, John
AU - Roalstad, Shelly
AU - Casper, T. Charles
AU - Shen, Ling
AU - Quach, Hong
AU - Quach, Diana
AU - Hillert, Jan
AU - Hedstrom, Anna
AU - Olsson, Tomas
AU - Kockum, Ingrid
AU - Alfredsson, Lars
AU - Schaefer, Catherine
AU - Barcellos, Lisa F.
AU - Waubant, Emmanuelle
N1 - Publisher Copyright:
© The Author(s), 2017.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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 <18 years (n = 569) and controls (n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases (n = 7588). Results: HLA–DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p < 2.0 × 10−16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated (p < 0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (ORavg = 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 < 2.0 × 10−16) 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.
AB - 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 <18 years (n = 569) and controls (n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases (n = 7588). Results: HLA–DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p < 2.0 × 10−16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated (p < 0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (ORavg = 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 < 2.0 × 10−16) 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.
KW - Multiple sclerosis
KW - epidemiology
KW - genetics
KW - pediatrics
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U2 - 10.1177/1352458517733551
DO - 10.1177/1352458517733551
M3 - Article
C2 - 28980494
AN - SCOPUS:85043377115
SN - 1352-4585
VL - 24
SP - 1825
EP - 1834
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
IS - 14
ER -