{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:17:35Z","timestamp":1792113455983,"version":"4.4.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013301","name":"Parkinson\u2019s Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013301","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson\u2019s disease; however, individuals with Parkinson\u2019s disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson\u2019s disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson\u2019s disease.<\/jats:p>\n                  <jats:p>PD GENEration is an ongoing multi-centre, observational study (NCT04057794, NCT04994015) offering genetic testing with results disclosure and genetic counselling to those in the US (including Puerto Rico), Canada and the Dominican Republic, through local clinical sites or remotely through self-enrolment. DNA samples are analysed by next-generation sequencing including deletion\/duplication analysis (Fulgent Genetics) with targeted testing of seven major Parkinson\u2019s disease-related genes. Variants classified as pathogenic\/likely pathogenic\/risk variants are disclosed to all tested participants by either neurologists or genetic counsellors. Demographic and clinical features are collected at baseline visits.<\/jats:p>\n                  <jats:p>Between September 2019 and June 2023, the study enrolled 10 510 participants across &amp;gt;85 centres, with 8301 having received results. Participants were: 59% male; 86% White, 2% Asian, 4% Black\/African American, 9% Hispanic\/Latino; mean age 67.4 \u00b1 10.8 years. Reportable genetic variants were observed in 13% of all participants, including 18% of participants with one or more \u2018high risk factors\u2019 for a genetic aetiology: early onset (&amp;lt;50 years), high-risk ancestry (Ashkenazi Jewish\/Basque\/North African Berber), an affected first-degree relative; and, importantly, in 9.1% of people with none of these risk factors. Reportable variants in GBA1 were identified in 7.7% of all participants; 2.4% in LRRK2; 2.1% in PRKN; 0.1% in SNCA; and 0.2% in PINK1, PARK7 or VPS35 combined. Variants in more than one of the seven genes were identified in 0.4% of participants.<\/jats:p>\n                  <jats:p>Approximately 13% of study participants had a reportable genetic variant, with a 9% yield in people with no high-risk factors. This supports the promotion of universal access to genetic testing for Parkinson\u2019s disease, as well as therapeutic trials for GBA1 and LRRK2-related Parkinson\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awae142","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T08:39:19Z","timestamp":1715243959000},"page":"2668-2679","source":"Crossref","is-referenced-by-count":117,"title":["Parkinson\u2019s disease variant detection and disclosure: PD GENEration, a North American study"],"prefix":"10.1093","volume":"147","author":[{"given":"Lola","family":"Cook","sequence":"first","affiliation":[{"name":"Medical and Molecular Genetics, Indiana University School of Medicine , Indianapolis, IN 46202 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Verbrugge","sequence":"additional","affiliation":[{"name":"Medical and Molecular Genetics, Indiana University School of Medicine , Indianapolis, IN 46202 , 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