• Zahra Nasr, Vinicius Andreoli Schoeps, Amin Ziaei, Akash Virupakshaiah, Cameron Adams, T Charles Casper, Michael Waltz, John Rose, Moses Rodriguez, Jan-Mendelt Tillema, Tanuja Chitnis, Jennifer S Graves, Leslie Benson, Mary Rensel, Lauren Krupp, Amy T Waldman, Bianca Weinstock-Guttman, Tim Lotze, Benjamin Greenberg, Gregory Aaen, Soe Mar, Teri Schreiner, Janace Hart, Steve Simpson-Yap, Clementina Mesaros, Lisa F Barcellos, and Emmanuelle Waubant.
• UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA.
• J. Neurol. Neurosurg. Psychiatr. 2023 Jul 1; 94 (7): 518525518-525.

BackgroundWe previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis.MethodsUsing a case-control paediatric multiple sclerosis study, gene-environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis was estimated.Genetic risk factors of interest included the two major HLA multiple sclerosis risk factors, the presence of DRB1*15 and the absence of A*02, and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including IL-6 (rs2069852), BCL-2 (rs2187163) and NFKB1 (rs7665090).Results490 paediatric-onset multiple sclerosis cases and 716 controls were included in the analyses. Exposures to insect repellent for ticks or mosquitos (OR 1.47, 95% CI 1.06 to 2.04, p=0.019), weed control products (OR 2.15, 95% CI 1.51 to 3.07, p<0.001) and plant/tree insect or disease control products (OR 3.25, 95% CI 1.92 to 5.49, p<0.001) were associated with increased odds of paediatric-onset multiple sclerosis. There was significant additive interaction between exposure to weed control products and NFKB1 SNP GG (attributable proportions (AP) 0.48, 95% CI 0.10 to 0.87), and exposure to plant or disease control products and absence of HLA-A*02 (AP 0.56; 95% CI 0.03 to 1.08). There was a multiplicative interaction between exposure to weed control products and NFKB1 SNP GG genotype (OR 2.30, 95% CI 1.00 to 5.30) but not for other exposures and risk variants. No interactions were found with IL-6 and BCL-2 SNP GG genotypes.ConclusionsThe presence of gene-environment interactions with household toxins supports their possible causal role in paediatric-onset multiple sclerosis.© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

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