Genetic risk factors for pediatric-onset multiple sclerosis

Mult Scler. 2018 Dec;24(14):1825-1834. doi: 10.1177/1352458517733551. Epub 2017 Oct 5.


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.

Keywords: Multiple sclerosis; epidemiology; genetics; pediatrics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Logistic Models
  • Male
  • Multiple Sclerosis / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Sweden


  • HLA-DRB1 Chains