{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T12:33:56Z","timestamp":1791722036927,"version":"4.3.4"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Genome-wide association studies have identified &amp;gt;230 genetic variants associated with susceptibility to multiple sclerosis and one genome-wide significant variant associated with progression of multiple sclerosis. Environmental risk factors, such as vitamin D deficiency and obesity, have also been implicated in multiple sclerosis pathogenesis. Statistical approaches building on these genetic data, such as Mendelian randomization and co-localization, have established putative causal links between environmental risk factors and multiple sclerosis risk, most notably for vitamin D and body mass index. However, studies have thus far revealed limited statistically significant interactions between host genetics and environmental factors beyond the major histocompatibility complex.<\/jats:p>\n                  <jats:p>Epigenetics (the study of non-nucleotide alterations to DNA, such as DNA methylation or histone acetylation) might provide a mechanistic framework for understanding how environmental and genetic factors interact in multiple sclerosis. Environmental factors, such as Epstein\u2013Barr virus infection, vitamin D deficiency and smoking, are associated with epigenetic modifications at key multiple sclerosis-related genomic loci, altering the expression of multiple sclerosis risk genes in a cell type-specific manner. Transcriptomics have identified significant pathways via which genetic risk is realized, potentially providing targets for intervention.<\/jats:p>\n                  <jats:p>This review synthesizes current evidence on gene\u2013environment interactions in the context of multiple sclerosis genome-wide association study findings, evaluates the strengths and limitations of various study methodologies, and discusses the challenges in elucidating the interplay between genetics and environmental factors. We propose potential strategies for future research to advance our understanding of the biological mechanisms underlying multiple sclerosis susceptibility in at-risk individuals.<\/jats:p>","DOI":"10.1093\/brain\/awag111","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:45:30Z","timestamp":1774529130000},"page":"2619-2628","source":"Crossref","is-referenced-by-count":3,"title":["Interplay between genetic and environmental risk factors in multiple sclerosis: what have we learned?"],"prefix":"10.1093","volume":"149","author":[{"given":"Benjamin M","family":"Jacobs","sequence":"first","affiliation":[{"name":"Centre for Preventive Neurology, Queen Mary University of London , London E1 4NS ,","place":["UK"]},{"name":"Department of Neurology, Royal London Hospital, Barts Health NHS Trust , London E1 1BB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijne","family":"Vandebergh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Antwerp , Antwerp 2610 ,","place":["Belgium"]},{"name":"VIB Center for Molecular Neurology, VIB , Antwerp 2610 ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3785-4742","authenticated-orcid":false,"given":"Vicki E","family":"Maltby","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Newcastle , Callaghan, NSW 2308 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2993-585X","authenticated-orcid":false,"given":"Ruth","family":"Dobson","sequence":"additional","affiliation":[{"name":"Centre for Preventive Neurology, Queen Mary University of London , London E1 4NS ,","place":["UK"]},{"name":"Department of Neurology, Royal London Hospital, Barts Health NHS Trust , London E1 1BB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2966-5335","authenticated-orcid":false,"given":"Karim L","family":"Kreft","sequence":"additional","affiliation":[{"name":"Academic Neurology, Academic Unit of Mental Health and Clinical Neurosciences, School of Medicine, University of Nottingham , Nottingham NG7 2UH ,","place":["UK"]},{"name":"Department of Neurology, Queen\u2019s Medical Centre, Nottingham University Hospitals NHS Trust , Nottingham NG7 2UH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"2026080312473117500_awag111-B1","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1093\/ntr\/ntae165","article-title":"Managing the exponential growth of Mendelian randomization 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