{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T19:32:18Z","timestamp":1783452738773,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,4]]},"group-title":"Neurology","reference-count":27,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    <jats:italic>LRRK2<\/jats:italic>\n                    variants are major contributors to Parkinson\u2019s disease (PD). Many pathogenic variants increase kinase activity, underscoring the value of functional assays in nominating therapeutic targets and kinase inhibitors as potential disease-modifying therapies.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To develop an interactive resource that provides functional context and ancestry-specific variant frequencies.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Genotyping and short-read sequencing data were analyzed for 101,678 individuals (61,709 PD, 39,969 controls) from the Global Parkinson\u2019s Genetics Program (GP2) and integrated with clinical and in-vitro biochemical kinase activity information.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:italic>LRRK2<\/jats:italic>\n                    Browser (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/gp2.org\/lrrk2browser\">http:\/\/gp2.org\/lrrk2browser<\/jats:ext-link>\n                    ) displays ancestry-specific genetic data for 19,596\n                    <jats:italic>LRRK2<\/jats:italic>\n                    variants (968 exonic, 14 disease-associated) across 11 populations, and functional data for 171 variants. Clinical annotations include age, age at onset, and family history of PD.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>\n                    The publicly available\n                    <jats:italic>LRRK2<\/jats:italic>\n                    Browser represents an open-access, multi-ancestry resource to support\n                    <jats:italic>LRRK2<\/jats:italic>\n                    variant interpretation. It aims to enhance the translational potential of genetic and functional data for precision medicine and the implementation of gene-targeted therapies in diverse populations.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.01.26357034","type":"posted-content","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T15:15:13Z","timestamp":1783178113000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>LRRK2<\/i>\n                  in Focus: A Global Browser Linking Genetic Diversity to Functional Effects"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7278-0347","authenticated-orcid":false,"given":"Spencer M.","family":"Grant","sequence":"first","affiliation":[{"name":"Center for Alzheimer\u2019s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"},{"name":"Department of Clinical Neurosciences, School of Clinical Medicine, The University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"van Midden","sequence":"additional","affiliation":[{"name":"University Medical Centre Ljubljana, Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Fernandez-Toledo","sequence":"additional","affiliation":[{"name":"University of Concepci\u00f3n, Concepci\u00f3n, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momodou","family":"Cham","sequence":"additional","affiliation":[{"name":"Richard Novati Catholic Hospital, Sogakope, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-7116","authenticated-orcid":false,"given":"Esther","family":"Sammler","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Faculty of Health, University of Dundee, Dundee, UK"},{"name":"Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Faculty of Life Sciences, University of Dundee, Dundee, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario R.","family":"Alessi","sequence":"additional","affiliation":[{"name":"Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Faculty of Life Sciences, University of Dundee, Dundee, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Global Parkinson\u2019s Genetics Program","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5473-3774","authenticated-orcid":false,"given":"Huw R.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK"},{"name":"UCL Movement Disorders Centre, University College London, London, 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