{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T11:46:10Z","timestamp":1775043970740,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,18]]},"group-title":"Genetic and Genomic Medicine","reference-count":34,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Variants in\n                    <jats:italic>GBA1<\/jats:italic>\n                    are important genetic risk factors for synucleinopathies, including Parkinson\u2019s disease (PD). While several\n                    <jats:italic>GBA1<\/jats:italic>\n                    variants are established risk or severity modifiers, the role of the p.E427K variant remains unclear.\n                  <\/jats:p>\n                  <jats:p>Objective<\/jats:p>\n                  <jats:p>\n                    To determine whether the\n                    <jats:italic>GBA1<\/jats:italic>\n                    p.E427K variant is associated with risk of synucleinopathies.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We performed a meta-analysis of case-control studies reporting the frequency of\n                    <jats:italic>GBA1<\/jats:italic>\n                    p.E427K (p.E388K) in PD and related synucleinopathies. Data were obtained from published studies, open-access resources, and large cohorts, including in-house datasets. Odds ratios (ORs) were calculated for each cohort and pooled using a random-effects model.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Across 67,484 patients and 124,079 controls,\n                    <jats:italic>GBA1<\/jats:italic>\n                    p.E427K was associated with increased disease risk (pooled OR = 1.87, 95% CI 1.28\u20132.72, P = 0.001). Enzymatic data showed reduced glucocerebrosidase activity in carriers.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:italic>GBA1<\/jats:italic>\n                    p.E427K variant is a risk factor for synucleinopathies and should be considered in genetic studies and clinical trials.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.18.26347268","type":"posted-content","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T22:50:15Z","timestamp":1773874215000},"source":"Crossref","is-referenced-by-count":0,"title":["The\n                  <i>GBA1<\/i>\n                  p.E427K (p.E388K) Variant is a Risk Factor for Synucleinopathies: A Meta-Analysis"],"prefix":"10.64898","author":[{"given":"Leah V.","family":"Chifamba","sequence":"first","affiliation":[{"name":"The 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