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Genome-wide Association and Meta-analysis of Age at Onset in Parkinson Disease: Evidence From the COURAGE-PD Consortium
DC Field | Value | Language |
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dc.contributor.author | 김윤중 | - |
dc.date.accessioned | 2023-03-21T07:31:50Z | - |
dc.date.available | 2023-03-21T07:31:50Z | - |
dc.date.issued | 2022-08 | - |
dc.identifier.issn | 0028-3878 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/193424 | - |
dc.description.abstract | Background and objectives: Considerable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on the AAO of PD; these have not been independently replicated. This study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations. Methods: A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC). Results: The COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9%: Europeans and 9.1%: East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance (p < 5 × 10-8). Nevertheless, the COURAGE-PD dataset confirmed the role of the previously published TMEM175 variant as a genetic determinant of the AAO of PD with Bonferroni-corrected nominal levels of significance (p < 0.025): (rs34311866: β(SE)COURAGE = 0.477(0.203), p COURAGE = 0.0185). The subsequent meta-analysis of COURAGE-PD and IPDGC datasets (Ntotal = 25,950) led to the identification of 2 genome-wide significant association signals on Chr 4, including the previously reported SNCA locus (rs983361: β(SE)COURAGE+IPDGC = 0.720(0.122), p COURAGE+IPDGC = 3.13 × 10-9) and a novel BST1 locus (rs4698412: β(SE)COURAGE+IPDGC = -0.526(0.096), p COURAGE+IPDGC = 4.41 × 10-8). Discussion: Our study further refines the genetic architecture of Chr 4 underlying the AAO of the PD phenotype through the identification of BST1 as a novel AAO PD locus. These findings open a new direction for the development of treatments to delay the onset of PD.. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Lippincott Williams & Wilkins | - |
dc.relation.isPartOf | NEUROLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Age of Onset | - |
dc.subject.MESH | Courage* | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Genetic Predisposition to Disease / genetics | - |
dc.subject.MESH | Genome-Wide Association Study | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Parkinson Disease* / epidemiology | - |
dc.subject.MESH | Parkinson Disease* / genetics | - |
dc.subject.MESH | Polymorphism, Single Nucleotide | - |
dc.title | Genome-wide Association and Meta-analysis of Age at Onset in Parkinson Disease: Evidence From the COURAGE-PD Consortium | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Neurology (신경과학교실) | - |
dc.contributor.googleauthor | Sandeep Grover | - |
dc.contributor.googleauthor | Ashwin Ashok Kumar Sreelatha | - |
dc.contributor.googleauthor | Lasse Pihlstrom | - |
dc.contributor.googleauthor | Cloé Domenighetti | - |
dc.contributor.googleauthor | Claudia Schulte | - |
dc.contributor.googleauthor | Pierre-Emmanuel Sugier | - |
dc.contributor.googleauthor | Milena Radivojkov-Blagojevic | - |
dc.contributor.googleauthor | Peter Lichtner | - |
dc.contributor.googleauthor | Océane Mohamed | - |
dc.contributor.googleauthor | Berta Portugal | - |
dc.contributor.googleauthor | Zied Landoulsi | - |
dc.contributor.googleauthor | Patrick May | - |
dc.contributor.googleauthor | Dheeraj Bobbili | - |
dc.contributor.googleauthor | Connor Edsall | - |
dc.contributor.googleauthor | Felix Bartusch | - |
dc.contributor.googleauthor | Maximilian Hanussek | - |
dc.contributor.googleauthor | Jens Krüger | - |
dc.contributor.googleauthor | Dena G Hernandez | - |
dc.contributor.googleauthor | Cornelis Blauwendraat | - |
dc.contributor.googleauthor | George D Mellick | - |
dc.contributor.googleauthor | Alexander Zimprich | - |
dc.contributor.googleauthor | Walter Pirker | - |
dc.contributor.googleauthor | Manuela Tan | - |
dc.contributor.googleauthor | Ekaterina Rogaeva | - |
dc.contributor.googleauthor | Anthony Lang | - |
dc.contributor.googleauthor | Sulev Koks | - |
dc.contributor.googleauthor | Pille Taba | - |
dc.contributor.googleauthor | Suzanne Lesage | - |
dc.contributor.googleauthor | Alexis Brice | - |
dc.contributor.googleauthor | Jean-Christophe Corvol | - |
dc.contributor.googleauthor | Marie-Christine Chartier-Harlin | - |
dc.contributor.googleauthor | Eugenie Mutez | - |
dc.contributor.googleauthor | Kathrin Brockmann | - |
dc.contributor.googleauthor | Angela B Deutschländer | - |
dc.contributor.googleauthor | Georges M Hadjigeorgiou | - |
dc.contributor.googleauthor | Efthimos Dardiotis | - |
dc.contributor.googleauthor | Leonidas Stefanis | - |
dc.contributor.googleauthor | Athina Maria Simitsi | - |
dc.contributor.googleauthor | Enza Maria Valente | - |
dc.contributor.googleauthor | Simona Petrucci | - |
dc.contributor.googleauthor | Letizia Straniero | - |
dc.contributor.googleauthor | Anna Zecchinelli | - |
dc.contributor.googleauthor | Gianni Pezzoli | - |
dc.contributor.googleauthor | Laura Brighina | - |
dc.contributor.googleauthor | Carlo Ferrarese | - |
dc.contributor.googleauthor | Grazia Annesi | - |
dc.contributor.googleauthor | Andrea Quattrone | - |
dc.contributor.googleauthor | Monica Gagliardi | - |
dc.contributor.googleauthor | Lena F Burbulla | - |
dc.contributor.googleauthor | Hirotaka Matsuo | - |
dc.contributor.googleauthor | Yusuke Kawamura | - |
dc.contributor.googleauthor | Nobutaka Hattori | - |
dc.contributor.googleauthor | Kenya Nishioka | - |
dc.contributor.googleauthor | Sun Ju Chung | - |
dc.contributor.googleauthor | Yun Joong Kim | - |
dc.contributor.googleauthor | Lukas Pavelka | - |
dc.contributor.googleauthor | Bart P C van de Warrenburg | - |
dc.contributor.googleauthor | Bastiaan R Bloem | - |
dc.contributor.googleauthor | Andrew B Singleton | - |
dc.contributor.googleauthor | Jan Aasly | - |
dc.contributor.googleauthor | Mathias Toft | - |
dc.contributor.googleauthor | Leonor Correia Guedes | - |
dc.contributor.googleauthor | Joaquim J Ferreira | - |
dc.contributor.googleauthor | Soraya Bardien | - |
dc.contributor.googleauthor | Jonathan Carr | - |
dc.contributor.googleauthor | Eduardo Tolosa | - |
dc.contributor.googleauthor | Mario Ezquerra | - |
dc.contributor.googleauthor | Pau Pastor | - |
dc.contributor.googleauthor | Monica Diez-Fairen | - |
dc.contributor.googleauthor | Karin Wirdefeldt | - |
dc.contributor.googleauthor | Nancy L Pedersen | - |
dc.contributor.googleauthor | Caroline Ran | - |
dc.contributor.googleauthor | Andrea C Belin | - |
dc.contributor.googleauthor | Andreas Puschmann | - |
dc.contributor.googleauthor | Clara Hellberg | - |
dc.contributor.googleauthor | Carl E Clarke | - |
dc.contributor.googleauthor | Karen E Morrison | - |
dc.contributor.googleauthor | Dimitri Krainc | - |
dc.contributor.googleauthor | Matt J Farrer | - |
dc.contributor.googleauthor | Rejko Kruger | - |
dc.contributor.googleauthor | Alexis Elbaz | - |
dc.contributor.googleauthor | Thomas Gasser | - |
dc.contributor.googleauthor | Manu Sharma | - |
dc.identifier.doi | 10.1212/WNL.0000000000200699 | - |
dc.contributor.localId | A00796 | - |
dc.relation.journalcode | J02340 | - |
dc.identifier.eissn | 1526-632X | - |
dc.identifier.pmid | 35970579 | - |
dc.contributor.alternativeName | Kim, Yun Joong | - |
dc.contributor.affiliatedAuthor | 김윤중 | - |
dc.citation.volume | 99 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | E698 | - |
dc.citation.endPage | E710 | - |
dc.identifier.bibliographicCitation | NEUROLOGY, Vol.99(7) : E698-E710, 2022-08 | - |
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