{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:03:53Z","timestamp":1790964233588,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The most common genetic risk factor for Parkinson's disease known is a damaging variant in the <jats:italic>GBA1<\/jats:italic> gene. The entire <jats:italic>GBA1<\/jats:italic> gene has rarely been studied in a large cohort from a single population. The objective of this study was to assess the entire <jats:italic>GBA1<\/jats:italic> gene in Parkinson's disease from a single large population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The <jats:italic>GBA1<\/jats:italic> gene was assessed in 3402 Dutch Parkinson's disease patients using next\u2010generation sequencing. Frequencies were compared with Dutch controls (n = 655). Family history of Parkinson's disease was compared in carriers and noncarriers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifteen percent of patients had a <jats:italic>GBA1<\/jats:italic> nonsynonymous variant (including missense, frameshift, and recombinant alleles), compared with 6.4% of controls (OR, 2.6; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Eighteen novel variants were detected. Variants previously associated with Gaucher's disease were identified in 5.0% of patients compared with 1.5% of controls (OR, 3.4; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). The rarely reported complex allele p.D140H\u2009+\u2009p.E326K appears to likely be a Dutch founder variant, found in 2.4% of patients and 0.9% of controls (OR, 2.7; <jats:italic>P<\/jats:italic> = 0.012). The number of first\u2010degree relatives (excluding children) with Parkinson's disease was higher in p.D140H\u2009+\u2009p.E326K carriers (5.6%, 21 of 376) compared with p.E326K carriers (2.9%, 29 of 1014); OR, 2.0; <jats:italic>P<\/jats:italic> = 0.022, suggestive of a dose effect for different <jats:italic>GBA1<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Dutch Parkinson's disease patients display one of the largest frequencies of <jats:italic>GBA1<\/jats:italic> variants reported so far, consisting in large part of the mild p.E326K variant and the more severe Dutch p.D140H\u2009+\u2009p.E326K founder allele. \u00a9 2020 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28112","type":"journal-article","created":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T02:35:15Z","timestamp":1593743715000},"page":"1667-1674","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["A <scp>Large\u2010Scale<\/scp> Full <scp><i>GBA1<\/i><\/scp> Gene Screening in Parkinson's Disease in the Netherlands"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-7978","authenticated-orcid":false,"given":"Jonas M.","family":"den Heijer","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie C.","family":"Cullen","sequence":"additional","affiliation":[{"name":"Lysosomal Therapeutics Inc  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marialuisa","family":"Quadri","sequence":"additional","affiliation":[{"name":"Erasmus Medical Center  Rotterdam The Netherlands"},{"name":"Janssen Vaccines and Prevention  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnoud","family":"Schmitz","sequence":"additional","affiliation":[{"name":"GenomeScan B.V.  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana C.","family":"Hilt","sequence":"additional","affiliation":[{"name":"Lysosomal Therapeutics Inc  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lansbury","sequence":"additional","affiliation":[{"name":"Lysosomal Therapeutics Inc  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk W.","family":"Berendse","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilma D.J.","family":"van de Berg","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob M.A.","family":"de Bie","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Boertien","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnita J.W.","family":"Boon","sequence":"additional","affiliation":[{"name":"Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0312-184X","authenticated-orcid":false,"given":"M. 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