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 Wheeler; John Rose; Nikita Melani Shukla; Lisa F Barcellos; Robyn Lucas; Emmanuelle Waubant

doi:10.1016/j.msard.2023.105351

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

Mult Scler Relat Disord. 2024 Feb:82:105351. doi: 10.1016/j.msard.2023.105351. Epub 2023 Dec 8.

Authors

Zahra Nasr¹, Akash Virupakshaiah², Vinicius Andreoli Schoeps², Nicolas Cherbuin³, T Charles Casper⁴, Michael Waltz⁴, Janace Hart², Moses Rodriguez⁵, Mark P Gorman⁶, Leslie A Benson⁶, Tanuja Chitnis⁷, Mary Rensel⁸, Aaron Abrams⁸, Lauren Krupp⁹, Amy T Waldman¹⁰, Tim Lotze¹¹, Gregory S Aaen¹², Soe Mar¹³, Teri Schreiner¹⁴, Yolanda Wheeler¹⁵, John Rose¹⁶, Nikita Melani Shukla¹⁷, Lisa F Barcellos¹⁸, Robyn Lucas¹⁹, Emmanuelle Waubant²

Affiliations

¹ UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA. Electronic address: emmanuelle.waubant@ucsf.edu.
² UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
³ Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, Australia.
⁴ University of Utah School of Medicine, Salt Lake City, Utah, USA.
⁵ Mayo Clinic, Rochester, Minnesota, USA.
⁶ Boston Childrens Hospital, Boston, Massachusetts, USA.
⁷ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Cleveland Clinic, Cleveland, Ohio, USA.
⁹ New York University Medical Center, New York City, New York, USA.
¹⁰ Division of Child Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
¹¹ Texas Children's Hospital, Houston, Texas, USA.
¹² Loma Linda University Children's Hospital, Loma Linda, California, USA.
¹³ Washington University in St. Louis, St Louis, Missouri, USA.
¹⁴ Childrens Hospital Colorado/University of Colorado, Aurora, Colorado, USA.
¹⁵ Children's Hospital of Alabama, Birmingham, Alabama, USA.
¹⁶ George E. Wahlen Department of Veterans Affairs Medical Center, University of Utah, Salt Lake City, UT, USA.
¹⁷ Baylor College of Medicine/Texas Children's Hospital, Neurology and Developmental Neuroscience, Houston, Texas, USA.
¹⁸ Genetic Epidemiology and Genomics Laboratory, Divisions of Epidemiology and Biostatistics, School of Public Health, University of California Berkeley, Berkeley, California, USA.
¹⁹ National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia.

PMID: 38141560
DOI: 10.1016/j.msard.2023.105351

Abstract

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.

Keywords: Gene-environment interactions; Multiple sclerosis; Risk factors; Time spent outdoors.

MeSH terms

Case-Control Studies
Child
Gene-Environment Interaction*
Humans
Multiple Sclerosis* / etiology
Multiple Sclerosis* / genetics
Risk Factors
Ultraviolet Rays / adverse effects