{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T06:03:27Z","timestamp":1779775407726,"version":"3.53.1"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018231","name":"Aligning Science Across Parkinson's","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018231","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      The objective of this study was to elucidate differences in the cumulative incidence of Leucine\u2010rich repeat kinase 2 (LRRK2) p.Gly2019Ser\n                      <jats:italic>\u2010<\/jats:italic>\n                      related Parkinson's disease (PD;\n                      <jats:italic>LRRK2<\/jats:italic>\n                      \u2010PD) between ancestries and countries.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 922 unrelated p.Gly2019Ser variant carriers (affected\u2009=\u2009762 and unaffected\u2009=\u2009160) from the Global Parkinson's Genetics Program (GP2) in addition to cohorts recruited from the Israeli Ashkenazi Jewish and Tunisian Arab\u2010Berber population. Cox proportional hazard models were applied to examine differences in cumulative incidence across ancestry groups and countries. All analyses were adjusted for biological sex and were exploratory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The median age at onset (AAO) of\n                      <jats:italic>LRRK2<\/jats:italic>\n                      \u2010PD was 5\u2009years younger in the North African (hazard ratio [HR]\u2009=\u20091.48, 95% confidence interval [CI]\u2009=\u20091.18\u20131.86,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20097.0\u2009\u00d7\u200910\n                      <jats:sup>\u22124<\/jats:sup>\n                      ) compared with the European ancestry group. In contrast, the median AAO was 5\u2009years older in the Ashkenazi Jewish (HR\u2009=\u20090.61, 95% CI\u2009=\u20090.50\u20130.75,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20094.0\u2009\u00d7\u200910\n                      <jats:sup>\u22126<\/jats:sup>\n                      ) compared with the European ancestry group. Additionally, patients from Israel (HR\u2009=\u20091.59, 95% CI\u2009=\u20091.30\u20131.39,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20094.0\u2009\u00d7\u200910\n                      <jats:sup>\u22126<\/jats:sup>\n                      ) and Tunisia (HR\u2009=\u20092.57, 95% CI: 2.16\u20133.06,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20092.0\u2009\u00d7\u200910\n                      <jats:sup>\u221216<\/jats:sup>\n                      ) had a median 5\u2010year and 10\u2010year younger AAO compared with patients from the United States, respectively. Last, when focusing only on individuals with an Ashkenazi Jewish background, patients from Israel still had a younger AAO than those from the United States (HR\u2009=\u20091.82, 95% CI\u2009=\u20091.48\u20132.24,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.5\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      ). Analogously, assessing only patients from the United States, the Ashkenazi Jewish ancestry group still had an older AAO than the European ancestry group (HR\u2009=\u20090.51, 95% CI\u2009=\u20090.39\u20130.67,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.3\u2009\u00d7\u200910\n                      <jats:sup>\u22126<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Our results provide evidence that a person's genetic ancestry and country of origin are associated with the AAO of\n                      <jats:italic>LRRK2<\/jats:italic>\n                      \u2010PD. This highlights the potential impact of both genetic and environmental factors on\n                      <jats:italic>LRRK2<\/jats:italic>\n                      \u2010PD AAO. ANN NEUROL 2026;99:1394\u20131404\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78181","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:48:32Z","timestamp":1773006512000},"page":"1394-1404","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Age at Onset of\n                    <scp>LRRK2<\/scp>\n                    p.\n                    <scp>Gly2019Ser<\/scp>\n                    Parkinson's Disease Across Ancestries and Countries of Origin"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0458-0498","authenticated-orcid":false,"given":"Theresa","family":"L\u00fcth","sequence":"first","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck 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