{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:53:50Z","timestamp":1790618030217,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003510","name":"Haridus- ja Teadusministeerium","doi-asserted-by":"publisher","award":["TK214"],"award-info":[{"award-number":["TK214"]}],"id":[{"id":"10.13039\/501100003510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["2014\u20102020.4.01.15\u20100012 GENTRANSMED"],"award-info":[{"award-number":["2014\u20102020.4.01.15\u20100012 GENTRANSMED"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Dopaminergic neuron depletion in the substantia nigra (SN) and the pathological aggregation of \u03b1\u2010synuclein are the neuropathological hallmarks of Parkinson's disease (PD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study aimed to investigate the association between the polygenic risk score for PD (PD\u2010PRS) and transcranial sonography (TCS)\u2010measured SN hyperechogenicity to enhance the accuracy of PD susceptibility prediction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PD\u2010PRSs were calculated for over 41,000 Estonian Biobank participants age 55+ years without a PD diagnosis. Participants in the highest and lowest PD\u2010PRS percentiles (n\u2009=\u2009222) underwent TCS measurements and Sniffin\u2019 sticks olfactory testing. A multivariable logistic regression model was used to examine the associations between PD\u2010PRS, risk and prodromal markers, and SN hyperechogenicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Data from 204 participants with TCS measurements were analyzed, including 107 individuals in the high\u2010risk PD\u2010PRS group and 97 in the low\u2010risk PD\u2010PRS group. Incorporating PD\u2010PRS group assignment improved the explained variance in SN hyperechogenicity from 17.2% to 31.9%. Participants in the low\u2010risk PD\u2010PRS group had 0.16 times lower odds (95% confidence interval (CI) =\u20090.07\u20130.35, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) of developing SN hyperechogenicity compared to high\u2010risk PD\u2010PRS individuals. Each unit increase in the Sniffin\u2019 sticks olfactory test score was significantly associated with reduced odds of SN hyperechogenicity (adjusted odds ratio\u2009=\u20090.60, 95% CI\u2009=\u20090.47\u20130.78, <jats:italic>P<\/jats:italic>\u2009=\u20090.002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings indicate that TCS\u2010measured SN hyperechogenicity is associated with PD\u2010PRS and olfactory impairment. This combined assessment may improve early diagnosis of prodromal PD by pinpointing individuals at increased risk.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mdc3.70011","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T23:42:58Z","timestamp":1741736578000},"page":"928-937","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Polygenic Risk Score Combined with Transcranial Sonography Refines Parkinson's Disease Risk Prediction"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2090-8780","authenticated-orcid":false,"given":"Mart","family":"Kals","sequence":"first","affiliation":[{"name":"Estonian Genome Center, Institute of Genomics University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anu","family":"Reigo","sequence":"additional","affiliation":[{"name":"Estonian Genome Center, Institute of Genomics University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maris","family":"Teder\u2010Laving","sequence":"additional","affiliation":[{"name":"Estonian Genome Center, Institute of Genomics University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariliis","family":"Vaht","sequence":"additional","affiliation":[{"name":"Estonian Genome Center, Institute of Genomics University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Estonian Biobank research team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiit","family":"Nikopensius","sequence":"additional","affiliation":[{"name":"Estonian Genome Center, Institute of Genomics University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Metspalu","sequence":"additional","affiliation":[{"name":"Estonian Genome Center, Institute of Genomics University of Tartu  Tartu Estonia"},{"name":"Institute of Molecular and Cell Biology University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toomas","family":"Toomsoo","sequence":"additional","affiliation":[{"name":"Confido Medical Centre  Tallinn Estonia"},{"name":"School of Natural Sciences and Health Tallinn University  Tallinn Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.13"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-019-0077-5"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23687"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae188"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae142"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30320-5"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01584-8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26431"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27802"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-323646"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.141"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25192"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-013-7171-0"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.108.059998"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.4172\/2155-9562.1000425"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultrasmedbio.2012.07.017"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000348595"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep20863"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2012.03798.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000960"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13550-015-0087-1"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12444"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222011234"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27281"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2022.04.017"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27616"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.0003"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2021.739571"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.4206"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12121859"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28761"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200115"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-024-00780-5"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt268"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09718-5"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940111001015"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2014.04.012"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26424"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3679"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1086\/521987"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.51"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26100"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11101030"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011743"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20232"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23644"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2017.01.006"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3753786"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21327"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2023.105815"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.12.008"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2014.12.021"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00405-2"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00404-0"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27035"}],"container-title":["Movement Disorders Clinical Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mdc3.70011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:29:15Z","timestamp":1760956155000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mdc3.70011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,28]]},"references-count":55,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/mdc3.70011"],"URL":"https:\/\/doi.org\/10.1002\/mdc3.70011","archive":["Portico"],"relation":{},"ISSN":["2330-1619","2330-1619"],"issn-type":[{"value":"2330-1619","type":"print"},{"value":"2330-1619","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,28]]},"assertion":[{"value":"2024-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}