{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:35:34Z","timestamp":1792787734858,"version":"4.5.0"},"reference-count":27,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100015415","name":"National MS Society, Upper Midwest Chapter","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015415","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CIHR","award":["DSEN Funding"],"award-info":[{"award-number":["DSEN Funding"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>One in 20 people using dimethyl fumarate (DMF), a commonly used disease-modifying therapy for multiple sclerosis (MS), develops severe lymphopenia. We aimed to identify genetic variation associated with DMF-related lymphopenia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Using a case\u2013control design, we included cases that had either grade 2 (absolute lymphocyte count &lt;0.8\u2009\u00d7\u200910\n                      <jats:sup>9<\/jats:sup>\n                      \/L) or 3 (&lt;0.5\u2009\u00d7\u200910\n                      <jats:sup>9<\/jats:sup>\n                      \/L) lymphopenia during DMF. Controls had normal lymphocyte counts and \u2a7e1\u2009year of DMF exposure. We generated a polygenic score for lymphocyte counts and evaluated its ability to predict DMF-associated lymphopenia in two cohorts, with adjustment for covariates. We also conducted a genome-wide association study (GWAS) and gene-based analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings:<\/jats:title>\n                    <jats:p>\n                      The discovery cohort comprised 238 PwMS of European genetic ancestry from Canada\/Australia (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200972 grade 2 cases, 34 grade 3 cases), and the replication cohort comprised 156 PwMS from Sweden (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200934 grade 2, 14 grade 3). A higher polygenic score for lymphocyte counts predicted reduced risk of grade 2 lymphopenia (hazard ratio\u2009=\u20090.43, 95% confidence interval: 0.25\u20130.73). The GWAS identified one locus associated with the minimum lymphocyte count during DMF (rs17087205, beta\u2009=\u2009\u22120.63, SE\u2009=\u20090.11,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20093.89e\u20138) but did not replicate (beta\u2009=\u2009\u22120.04,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.47).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Common polygenic variation of lymphocyte counts was significantly associated with moderate lymphopenia during DMF treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585261471335","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:34:46Z","timestamp":1787027686000},"page":"1292-1301","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lymphocyte count polygenicity underlies dimethyl fumarate\u2013associated lymphopenia in multiple sclerosis"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3928-9879","authenticated-orcid":false,"given":"Kaarina","family":"Kowalec","sequence":"first","affiliation":[{"name":"College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada; Department of Biochemistry &amp; Medical Genetics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada; Department of Medical Epidemiology &amp; Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-5762","authenticated-orcid":false,"given":"Ali","family":"Manouchehrinia","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada; Karolinska Neuroimmunology and Multiple Sclerosis Center, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1956-1700","authenticated-orcid":false,"given":"Elaine","family":"Kingwell","sequence":"additional","affiliation":[{"name":"Department of Primary Care and Population Health, Institute of Epidemiology and Health Care, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Carruthers","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1855-5595","authenticated-orcid":false,"given":"Ruth Ann","family":"Marrie","sequence":"additional","affiliation":[{"name":"Department of Medicine and Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada; Nova Scotia Health, Halifax, NS, Canada; Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charity","family":"Evans","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia","family":"Rotstein","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Neurology, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie J","family":"Kuan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhuo","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianne","family":"Desrochers","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3942-4340","authenticated-orcid":false,"given":"Vilija G","family":"Jokubaitis","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette","family":"Lechner-Scott","sequence":"additional","affiliation":[{"name":"Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia; Immune Health Research Program, Hunter Medical Research Institute, Newcastle, NSW, Australia"}],"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":"Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia; Immune Health Research Program, Hunter Medical Research Institute, Newcastle, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira","family":"Groen","sequence":"additional","affiliation":[{"name":"Immune Health Research Program, Hunter Medical Research Institute, Newcastle, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galen EB","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Medical Genetics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada; Department of Pharmacology and Therapeutics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; PrairieNeuro Research Centre, Kleysen Institute for Advanced Medicine, Health Sciences Centre and Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Children\u2019s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt I","family":"Dr\u00f6gem\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Medical Genetics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada; Children\u2019s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada; CancerCare Manitoba Research Institute, Winnipeg, MB, Canada; Centre on Aging, Winnipeg, MB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha","family":"Bernatsky","sequence":"additional","affiliation":[{"name":"Department of Medicine, Divisions of Clinical Epidemiology and Rheumatology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C","family":"Levin","sequence":"additional","affiliation":[{"name":"Office of the Saskatchewan Multiple Sclerosis Research Chair, Department of Medicine, Division of Neurology, College of Medicine, University of Saskatchewan, Saskatchewan, Saskatoon, SK, Canada; Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Knox","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah Al","family":"Maruf","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada; Children\u2019s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada; Department of Psychiatry, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Alfredsson","sequence":"additional","affiliation":[{"name":"Karolinska Neuroimmunology and Multiple Sclerosis Center, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7386-6732","authenticated-orcid":false,"given":"Jan","family":"Hillert","sequence":"additional","affiliation":[{"name":"Karolinska Neuroimmunology and Multiple Sclerosis Center, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0867-4726","authenticated-orcid":false,"given":"Ingrid","family":"Kockum","sequence":"additional","affiliation":[{"name":"Karolinska Neuroimmunology and Multiple Sclerosis Center, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Olsson","sequence":"additional","affiliation":[{"name":"Karolinska Neuroimmunology and Multiple Sclerosis Center, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4855-0039","authenticated-orcid":false,"given":"Pernilla","family":"Stridh","sequence":"additional","affiliation":[{"name":"Karolinska Neuroimmunology and Multiple Sclerosis Center, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klementy","family":"Shchetynsky","sequence":"additional","affiliation":[{"name":"Karolinska Neuroimmunology and Multiple Sclerosis Center, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristy","family":"Dever","sequence":"additional","affiliation":[{"name":"Edwin SH Leong Centre for Healthy Aging, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; 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