{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:16:32Z","timestamp":1780492592172,"version":"3.54.1"},"reference-count":36,"publisher":"BMJ","issue":"7","funder":[{"name":"NMSS","award":["HC-1509-06233"],"award-info":[{"award-number":["HC-1509-06233"]}]},{"DOI":"10.13039\/501100007459","name":"Multiple Sclerosis International Federation","doi-asserted-by":"publisher","award":["McDonald Grant"],"award-info":[{"award-number":["McDonald Grant"]}],"id":[{"id":"10.13039\/501100007459","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["R01NS071463"],"award-info":[{"award-number":["R01NS071463"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>We previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a case\u2013control paediatric multiple sclerosis study, gene\u2013environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis was estimated.<\/jats:p><jats:p>Genetic risk factors of interest included the two major HLA multiple sclerosis risk factors, the presence of<jats:italic>DRB1*15<\/jats:italic>and the absence of<jats:italic>A*02,<\/jats:italic>and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including<jats:italic>IL-6<\/jats:italic>(rs2069852),<jats:italic>BCL-2<\/jats:italic>(rs2187163) and<jats:italic>NFKB1<\/jats:italic>(rs7665090).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>490 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%\u2009CI 1.06 to 2.04, p=0.019), weed control products (OR 2.15, 95%\u2009CI 1.51 to 3.07, p&lt;0.001) and plant\/tree insect or disease control products (OR 3.25, 95%\u2009CI 1.92 to 5.49, p&lt;0.001) were associated with increased odds of paediatric-onset multiple sclerosis. There was significant additive interaction between exposure to weed control products and<jats:italic>NFKB1<\/jats:italic>SNP GG (attributable proportions (AP) 0.48, 95%\u2009CI 0.10 to 0.87), and exposure to plant or disease control products and absence of<jats:italic>HLA-A*02<\/jats:italic>(AP 0.56; 95%\u2009CI 0.03 to 1.08). There was a multiplicative interaction between exposure to weed control products and<jats:italic>NFKB1<\/jats:italic>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<jats:italic>IL-6<\/jats:italic>and<jats:italic>BCL-2<\/jats:italic>SNP GG genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The presence of gene\u2013environment interactions with household toxins supports their possible causal role in paediatric-onset multiple sclerosis.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2022-330713","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T18:26:12Z","timestamp":1675275972000},"page":"518-525","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Gene\u2013environment interactions increase the risk of paediatric-onset multiple sclerosis associated with household chemical 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