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Pharmacogenomics offers a promising avenue to identify genetic markers that, combined with clinico-demographic predictors, could enhance personalized therapeutic decisions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>This multi-center study investigated genetic determinants of response to interferon-beta (IFN-\u03b2) and glatiramer acetate (GA) in European ancestry patients with relapsing\u2013remitting MS (RRMS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>After harmonization and quality control, we tested over 6 million genetic variants. We used negative binomial regression, meta-analysis, and gene-set enrichment to link variants, genes, and biological pathways to treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In 679 GA and 1614 IFN-\u03b2 patients, the top GA variant was rs2053696A in MAP3\u2009K1 (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20093.97*10\n                      <jats:sup>\u22129<\/jats:sup>\n                      ), involved in key signaling pathways. Another significant GA signal was in WWOX. For IFN-\u03b2, no genome-wide significant variants were found, but suggestive signals emerged near ZMIZ1, ZCCHC7, and other genes linked to immune function and interferon signaling. Gene-set analysis revealed IL-17 regulation for GA and ion channel pathways for IFN-\u03b2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>This study identified novel genetic variants for GA response, implicating genes in crucial pathways. For IFN-\u03b2, suggestive signals point to immune and interferon-related genes. These findings enhance our understanding of genetic influences on RRMS treatment response, while highlighting pharmacogenomic research challenges.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585261417130","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:29:46Z","timestamp":1773224986000},"page":"747-758","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacogenomics of response to interferon-beta and glatiramer acetate in Multiple Sclerosis: A multi-centric study"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8573-1748","authenticated-orcid":false,"given":"Andrea","family":"Corona","sequence":"first","affiliation":[{"name":"Laboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, Milan, Italy; CRC \u201cAldo Ravelli\u201d for Experimental Brain Therapeutics, Department of Health Science, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9561-4360","authenticated-orcid":false,"given":"Ferdinando","family":"Clarelli","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Neurological Disorders, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimmo","family":"P\u00e4\u00e4kk\u00f6nen","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2616-7274","authenticated-orcid":false,"given":"Adil","family":"Harroud","sequence":"additional","affiliation":[{"name":"The Neuro (Montreal Neurological Institute-Hospital), Montr\u00e9al, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montr\u00e9al, QC, Canada; Department of Human Genetics, McGill University, Montr\u00e9al, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klementy","family":"Shchetynsky","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0908-7469","authenticated-orcid":false,"given":"Alen","family":"Zollo","sequence":"additional","affiliation":[{"name":"Laboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, Milan, Italy; CRC \u201cAldo Ravelli\u201d for Experimental Brain Therapeutics, Department of Health Science, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Mingione","sequence":"additional","affiliation":[{"name":"Laboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, Milan, Italy; 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Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5985-6784","authenticated-orcid":false,"given":"Bernhard","family":"Hemmer","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Goris","sequence":"additional","affiliation":[{"name":"Laboratory for Neuroimmunology, Department of Neurosciences, KU Leuven Brain Institute, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Dubois","sequence":"additional","affiliation":[{"name":"Laboratory for Neuroimmunology, Department of Neurosciences, KU Leuven Brain Institute, Leuven, Belgium; Department of Neurology, University Hospitals, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helle Bach","family":"S\u00f8ndergaard","sequence":"additional","affiliation":[{"name":"Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital\u2014Rigshospitalet, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finn","family":"Sellebjerg","sequence":"additional","affiliation":[{"name":"Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital\u2014Rigshospitalet, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"D\u2019alfonso","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Eastern Piedmont, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne Flinstad","family":"Harbo","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway; 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The latitude-dependent autoimmune disease risk genes ZMIZ1 and IRF8 regulate mononuclear phagocytic cell differentiation in response to vitamin D. 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