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Genetic variation at the\n                    <jats:italic>MOBP<\/jats:italic>\n                    locus has been associated with risk for multiple neurodegenerative disorders, including progressive supranuclear palsy (PSP), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Epigenetically,\n                    <jats:italic>MOBP<\/jats:italic>\n                    promoter hypermethylation and reduced expression have been reported in multiple system atrophy (MSA). Although\n                    <jats:italic>MOBP<\/jats:italic>\n                    is thought to play a role in oligodendrocyte morphology and myelin structure, how genetic and epigenetic variation at this locus influences gene regulation and contributes to disease risk remains poorly understood across neurodegenerative disorders.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We assessed genetic overlap and colocalisation at the\n                    <jats:italic>MOBP<\/jats:italic>\n                    locus across multiple neurodegenerative diseases. Disease-associated signals were fine-mapped to prioritise putative causal variants, and the strongest signals were subsequently investigated using molecular quantitative trait loci and post-mortem brain tissue datasets.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    ALS and PSP showed strong genetic association at\n                    <jats:italic>MOBP<\/jats:italic>\n                    , with highly overlapping associated variants and strong evidence that both diseases share the same causal signal. Overlap with frontotemporal dementia was weaker. Methylation quantitative trait locus colocalisation identified cg15069948, located near an exon junction within\n                    <jats:italic>MOBP<\/jats:italic>\n                    , as strongly colocalising with the ALS and PSP genetic risk signals. In PSP brain tissue, carriers of the rs1768208-T risk allele showed lower methylation at cg15069948. We additionally identified evidence for an interaction between rs1768208 genotype and cg15069948 methylation associated with altered\n                    <jats:italic>MOBP<\/jats:italic>\n                    3\u2032 untranslated region architecture.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    These findings identify a shared ALS\/PSP genetic\u2013epigenetic mechanism at\n                    <jats:italic>MOBP<\/jats:italic>\n                    that is distinct from promoter-associated dysregulation in MSA. Together, they position\n                    <jats:italic>MOBP<\/jats:italic>\n                    as a key oligodendrocyte regulatory locus with both shared and disea e-specific roles in neurodegeneration.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.25.714147","type":"posted-content","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T20:30:14Z","timestamp":1774643414000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic and epigenetic convergence at\n                  <i>MOBP<\/i>\n                  links ALS and PSP"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5289-0010","authenticated-orcid":false,"given":"Katherine","family":"Fodder","sequence":"first","affiliation":[{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megha","family":"Murthy","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6423-9983","authenticated-orcid":false,"given":"Joshua","family":"Harvey","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8964-0682","authenticated-orcid":false,"given":"Ehsan","family":"Pishva","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK"},{"name":"Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute (MHeNS), Maastricht University, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7570-6065","authenticated-orcid":false,"given":"Katie","family":"Lunnon","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-5704","authenticated-orcid":false,"given":"Towfique","family":"Raj","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn Genomics Institute, Estelle and Daniel Maggin Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Ronald M. Loeb Center for Alzheimer\u2019s Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt W","family":"Farrell","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Ronald M. 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