{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T22:44:20Z","timestamp":1777070660172,"version":"3.51.4"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002488","name":"Brookdale Foundation Group","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010785","name":"Canada First Research Excellence Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010785","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. 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However, the role of heterozygous\n PRKN<\/jats:italic>\n variants in the risk of PD is controversial.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n Our aim was to examine the association between heterozygous\n PRKN<\/jats:italic>\n variants, including single\u2010nucleotide variants and copy\u2010number variations (CNVs), and PD.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We fully sequenced\n PRKN<\/jats:italic>\n in 2809 PD patients and 3629 healthy controls, including 1965 late\u2010onset (63.97\u2009\u00b1\u20097.79\u2009years, 63% men) and 553 early\u2010onset PD patients (43.33\u2009\u00b1\u20096.59\u2009years, 68% men).\n PRKN<\/jats:italic>\n was sequenced using targeted next\u2010generation sequencing with molecular inversion probes. CNVs were identified using a combination of multiplex ligation\u2010dependent probe amplification and ExomeDepth. To examine whether rare heterozygous single\u2010nucleotide variants and CNVs in\n PRKN<\/jats:italic>\n are associated with PD risk and onset, we used optimized sequence kernel association tests and regression models.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We did not find any associations between all types of\n PRKN<\/jats:italic>\n variants and risk of PD. Pathogenic and likely\u2010pathogenic heterozygous single\u2010nucleotide variants and CNVs were less common among PD patients (1.52%) than among controls (1.8%, false discovery rate\u2010corrected\n P<\/jats:italic>\n =\u20090.55). No associations with age at onset and in stratified analyses were found.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Heterozygous single\u2010nucleotide variants and CNVs in\n PRKN<\/jats:italic>\n are not associated with PD. Molecular inversion probes allow for rapid and cost\u2010effective detection of all types of\n PRKN<\/jats:italic>\n variants, which may be useful for pretrial screening and for clinical and basic science studies targeting specifically\n PRKN<\/jats:italic>\n patients. \u00a9 2020 International Parkinson and Movement Disorder Society\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mds.28299","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T13:34:47Z","timestamp":1600954487000},"page":"178-187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Analysis of Heterozygous\n \n PRKN<\/i>\n <\/scp>\n Variants and Copy\u2010Number Variations in Parkinson's Disease"],"prefix":"10.1002","volume":"36","author":[{"given":"Eric","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Human Genetics McGill University Montr\u00e9al Quebec Canada"},{"name":"Montreal Neurological 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H.","family":"Waters","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Physicians and Surgeons Columbia University Medical Center New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lior","family":"Greenbaum","sequence":"additional","affiliation":[{"name":"The Danek Gertner Institute of Human Genetics, Sheba Medical Center Ramat Gan Israel"},{"name":"The Joseph Sagol Neuroscience Center, Sheba Medical Center Ramat Gan Israel"},{"name":"Sackler School of Medicine, Tel\u2010Aviv University Tel\u2010Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto J.","family":"Espay","sequence":"additional","affiliation":[{"name":"UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders Cincinnati Ohio 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