Gene-environment interactions and risk of pediatric-onset multiple sclerosis associated with time spent outdoors

Zahra Nasr, Akash Virupakshaiah, Vinicius Andreoli Schoeps, Nicolas Cherbuin, T. Charles Casper, Michael Waltz, Janace Hart, Moses Rodriguez, Mark P. Gorman, Leslie A. Benson, Tanuja Chitnis, Mary Rensel, Aaron Abrams, Lauren Krupp, Amy T. Waldman, Tim Lotze, Gregory S. Aaen, Soe Mar, Teri Schreiner, Yolanda WheelerJohn Rose, Nikita Melani Shukla, Lisa F. Barcellos, Robyn Lucas, Emmanuelle Waubant

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: Our previous study identified a significant association between lower time spent outdoors, as a proxy of sun exposure, and a higher risk of pediatric-onset multiple sclerosis (POMS). UV radiation modulates the expression of several genes, but it is unknown whether these genes modify the effect of sun exposure on POMS risk. Methods: In an age- and sex-matched case-control study, we evaluated the additive and multiplicative interactions between time spent outdoors and genetic non-HLA risk variants for developing POMS within the metabolic pathways of UV radiation, including CD28(rs6435203), CD86(rs9282641), and NFkB1(rs7665090) and the top two HLA risk factors (presence of DRB1×15 and absence of A*02). Results: In an adjusted model (332 POMS cases, 534 healthy controls), greater time compared to <30 min/day spent outdoors during the prior summer and higher UV radiation dose were associated with decreased odds of POMS (OR 0.66, 95% CI 0.56–0.78, p < 0.001; OR 0.78, 95 % CI 0.62–0.98, p = 0.04, respectively). No significant additive or multiplicative interactions were found between risk factors. Conclusions: The exploration of gene-environment interactions in the risk of developing MS can unravel the underlying mechanisms involved. Although we do not have evidence that our candidate genes contribute to interactions, other genes may.

Original languageEnglish
Article number105351
JournalMultiple Sclerosis and Related Disorders
StatePublished - Feb 2024


  • Gene-environment interactions
  • Multiple sclerosis
  • Risk factors
  • Time spent outdoors


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