{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T02:55:18Z","timestamp":1777604118708,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD 036071"],"award-info":[{"award-number":["HD 036071"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["IDDRC P50 HD103526"],"award-info":[{"award-number":["IDDRC P50 HD103526"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1172990"],"award-info":[{"award-number":["APP1172990"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["CF06\/0269"],"award-info":[{"award-number":["CF06\/0269"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Premutation alleles of the <jats:italic>FMR1<\/jats:italic> X\u2010linked gene containing CGG repeat expansions ranging from 55 to 200 are associated with diverse late\u2010onset neurological involvements, including most severe disorder termed Fragile X\u2010associated Tremor\/Ataxia Syndrome (FXTAS). It is intriguing that at least one\u2010third of male, and a much lower than predicted from the X\u2010linkage proportion of female carriers are free of this syndrome. This suggests the existence of secondary genetic factors modifying the risk of neurological involvements in these carriers. Considering the occasional presence of parkinsonian features in FXTAS, we explored the possibility that the Parkinson's Disease Polygenic Risk Score (PD PRS) is related to the occurrence of FXTAS or less severe neurological involvements, in premutation carriers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The Genome\u2010wide SNP genotyping and clinical data on neurological status were obtained from 250 unrelated affected and non\u2010affected male and female adult carriers of the premutation. The medians for the Parkinson\u2019s Disease Polygenic Risk Score (PD PRS) were compared between the groups of asymptomatic and neurologically affected carriers, and the association of PD PRS with neurological involvement in context with the other known risk factors was explored by fitting univariate and multiple logistic regression models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was a significant difference between the medians from the asymptomatic versus neurologically affected (FXTAS+) groups (<jats:italic>p<\/jats:italic>\u2009=\u20090.009). The FXTAS+ status was significantly associated with age at testing (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), gender (<jats:italic>p<\/jats:italic>\u2009=\u20090.026), and with PD PRS (<jats:italic>p<\/jats:italic>\u2009=\u20090.021). The contribution of PD PRS remained significant after adjusting for age and gender (<jats:italic>p<\/jats:italic>\u2009=\u20090.044).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We have obtained the first evidence for the relationship between PD PRS and the risk of FXTAS or lesser neurological involvements in the FMR1 premutation carriers. This suggests the role of Parkinson's disease polygenic variants as genetic modifiers of the risk of late onset neurological changes in these carriers.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70043","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T12:28:58Z","timestamp":1732624138000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Parkinson's Disease Polygenic Risk Score and Neurological Involvement in Carriers of the <scp><i>FMR1<\/i><\/scp> Premutation Allele: A Case for Genetic Modifier"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2180-2606","authenticated-orcid":false,"given":"Danuta Z.","family":"Loesch","sequence":"first","affiliation":[{"name":"School of Psychology and Public Health La Trobe University  Bundoora Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Freddy","family":"Chafota","sequence":"additional","affiliation":[{"name":"Mental Health &amp; Neuroscience Program QIMR Berghofer Medical Research Institute  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minh Q.","family":"Bui","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, School of Global and Population Health University of Melbourne  Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elsdon","family":"Storey","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neuroscience) Monash University, Alfred Hospital Campus  Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Atkinson","sequence":"additional","affiliation":[{"name":"School of Psychology and Public Health La Trobe University  Bundoora Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas G.","family":"Martin","sequence":"additional","affiliation":[{"name":"Mental Health &amp; Neuroscience Program QIMR Berghofer Medical Research Institute  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott D.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Mental Health &amp; Neuroscience Program QIMR Berghofer Medical Research Institute  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel E.","family":"Renter\u00eda","sequence":"additional","affiliation":[{"name":"Mental Health &amp; Neuroscience Program QIMR Berghofer Medical Research Institute  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randi J.","family":"Hagerman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California Davis Health  Sacramento California USA"},{"name":"Medical Investigation of Neurodevelopmental Disorders (MIND) Institute University of California Davis Health  Sacramento California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flora","family":"Tassone","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine University of California  Davis California USA"},{"name":"School of Medicine and MIND Institute University of California Davis Medical Center  Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"1757","article-title":"Fragile X Premutation Carriers: Characteristic MR Imaging Findings of Adult Male Patients With Progressive Cerebellar and Cognitive Dysfunction","volume":"23","author":"Brunberg J. A.","year":"2002","journal-title":"AJNR. American Journal of Neuroradiology"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124391"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43856-021-00046-8"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0b013e3181c35f25"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32060"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2007.00818.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.05.010"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2009.136101"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf184"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1086\/386296"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.1.127"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-31"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000091656"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.12449"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2008.04.037"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.4.460"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-010-0270-5"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.7.1002"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12653-0"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2005.00425.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-5434-2_6"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2021.10"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.577246"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20753"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2022.167932"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30320-5"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2014.01.006"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-9-53"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.12942"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2008.070073"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12182330"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20297"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.03.009"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70043","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T07:00:27Z","timestamp":1732690827000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70043"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":33,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/mgg3.70043"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70043","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70043"}}