Genetic risk factors for pediatric-onset multiple sclerosis

被引：35

作者：

Gianfrancesco, Milena A. ^{[1
]}

Stridh, Pernilla ^{[2
,3
,4
]}

Shao, Xiaorong ^{[1
]}

Rhead, Brooke ^{[5
]}

Graves, Jennifer S. ^{[6
]}

Chitnis, Tanuja ^{[7
]}

Waldman, Amy ^{[8
]}

Lotze, Timothy ^{[9
]}

Schreiner, Teri ^{[10
]}

Belman, Anita ^{[11
]}

Greenberg, Benjamin ^{[12
]}

Weinstock-Guttman, Bianca ^{[13
]}

Aaen, Gregory ^{[14
]}

Tillema, Jan M. ^{[15
]}

Hart, Janace ^{[6
,16
]}

Caillier, Stacy ^{[6
,16
]}

Ness, Jayne ^{[17
,18
]}

Harris, Yolanda ^{[17
,18
]}

Rubin, Jennifer ^{[19
]}

Candee, Meghan ^{[20
,21
]}

Krupp, Lauren ^{[11
]}

Gorman, Mark ^{[22
]}

Benson, Leslie ^{[22
]}

Rodriguez, Moses ^{[15
]}

Mar, Soe ^{[23
]}

Kahn, Ilana ^{[24
]}

Rose, John ^{[25
]}

Roalstad, Shelly ^{[26
]}

Casper, T. Charles ^{[26
]}

Shen, Ling ^{[27
]}

Quach, Hong ^{[1
]}

Quach, Diana ^{[1
]}

Hillert, Jan ^{[28
]}

Hedstrom, Anna ^{[28
]}

Olsson, Tomas ^{[2
,3
,4
]}

Kockum, Ingrid ^{[2
,3
,4
]}

Alfredsson, Lars ^{[28
,29
]}

Schaefer, Catherine ^{[27
,30
]}

Barcellos, Lisa F. ^{[5
,27
,31
]}

Waubant, Emmanuelle ^{[6
]}

机构：

[1] Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA

[2] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden

[3] Karolinska Inst, Ctr Mol Med, Stockholm, Sweden

[4] Karolinska Univ Hosp, Stockholm, Sweden

[5] Univ Calif Berkeley, Computat Biol Grad Grp, Berkeley, CA 94720 USA

[6] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA

[7] Massachusetts Gen Hosp Children, Partners Pediat Multiple Sclerosis Ctr, Boston, MA USA

[8] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA

[9] Baylor Coll Med, Blue Bird Circle Multiple Sclerosis Ctr, Houston, TX 77030 USA

[10] Univ Colorado, Childrens Hosp Colorado, Denver, CO 80202 USA

[11] Stony Brook Childrens Hosp, Lourie Ctr Pediat MS, Stony Brook, NY USA

[12] Univ Texas Southwestern, Dept Neurol & Neurotherapeut, Dallas, TX USA

[13] SUNY Buffalo, Jacobs Neurol Inst, Pediat Multiple Sclerosis Ctr, Buffalo, NY USA

[14] Loma Linda Univ, Childrens Hosp, Pediat MS Ctr, Loma Linda, CA 92350 USA

[15] Mayo Clin, Pediat MS Ctr, Rochester, MN USA

[16] Univ Calif San Francisco, Reg Pediat MS Ctr, San Francisco, CA 94143 USA

[17] Univ Alabama Birmingham, Ctr Pediat Onset Demyelinating Dis, Birmingham, AL USA

[18] Childrens Hosp Alabama, Birmingham, AL USA

[19] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Div Neurol, Chicago, IL 60611 USA

[20] Univ Utah, Salt Lake City, UT USA

[21] Primary Childrens Med Ctr, Salt Lake City, UT USA

[22] Boston Childrens Hosp, Boston, MA USA

[23] Washington Univ, Sch Med, Pediat Onset Demyelinating Dis & Autoimmune Encep, St Louis, MO USA

[24] Childrens Natl Med Ctr, Washington, DC 20010 USA

[25] Univ Utah, Sch Med, Dept Neurol, Salt Lake City, UT USA

[26] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA

[27] Kaiser Permanente, Div Res, Oakland, CA USA

[28] Karolinska Inst, Inst Environm Med IMM, Stockholm, Sweden

[29] Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden

[30] Kaiser Permanente, Res Program Genes Environm & Hlth, Oakland, CA USA

[31] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA

来源：

MULTIPLE SCLEROSIS JOURNAL | 2018年 / 24卷 / 14期

关键词：

Multiple sclerosis; genetics; epidemiology; pediatrics; LOCUS; AGE; HLA-DRB1-ASTERISK-1501; ASSOCIATION; CRITERIA; TIME; SNP; MS;

D O I：

10.1177/1352458517733551

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 x 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 x 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.

引用

页码：1825 / 1834

页数：10

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