دورية أكاديمية
Genome-wide Association and Meta-analysis of Age at Onset in Parkinson Disease: Evidence from the COURAGE-PD Consortium
| العنوان: | Genome-wide Association and Meta-analysis of Age at Onset in Parkinson Disease: Evidence from the COURAGE-PD Consortium |
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| المؤلفون: | Grover S., Sreelatha A.A.K., Pihlstrom L., Domenighetti C., Schulte C., Sugier P.-E., Radivojkov-Blagojevic M., Lichtner P., Mohamed O., Portugal B., Landoulsi Z., May P., Bobbili D., Edsall C., Bartusch F., Hanussek M., Krüger J., Hernandez D.G., Blauwendraat C., Mellick G.D., Zimprich A., Pirker W., Tan M., Rogaeva E., Lang A., Koks S., Taba P., Lesage S., Brice A., Corvol J.-C., Chartier-Harlin M.-C., Mutez E., Brockmann K., Deutschländer A.B., Hadjigeorgiou G.M., Dardiotis E., Stefanis L., Simitsi A.M., Valente E.M., Petrucci S., Straniero L., Zecchinelli A., Pezzoli G., Brighina L., Ferrarese C., Annesi G., Quattrone A., Gagliardi M., Burbulla L.F., Matsuo H., Kawamura Y., Hattori N., Nishioka K., Chung S.J., Kim Y.J., Pavelka L., Van De Warrenburg B.P.C., Bloem B.R., Singleton A.B., Aasly J., Toft M., Guedes L.C., Ferreira J.J., Bardien S., Carr J., Tolosa E., Ezquerra M., Pastor P., Diez-Fairen M., Wirdefeldt K., Pedersen N.L., Ran C., Belin A.C., Puschmann A., Hellberg C., Clarke C.E., Morrison K.E., Krainc D., Farrer M.J., Kruger R., Elbaz A., Gasser T., Sharma M. |
| المصدر: | Neurology ; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85136019610&doi=10.1212%2fWNL.0000000000200699&partnerID=40&md5=7766b3a0615ef70c6f2a5cd8fcdabd2aTest |
| سنة النشر: | 2022 |
| المجموعة: | University of Thessaly Institutional Repository / Ιδρυματικό Αποθετήριο Πανεπιστημίου Θεσσαλίας |
| مصطلحات موضوعية: | ADP ribosyl cyclase/cyclic ADP ribose hydrolase 1, adult, Article, BST1 gene, caudate nucleus, CD38 gene, chromosome 12, chromosome 4, chromosome 7, chromosome 8, controlled study, correlation analysis, expression quantitative trait locus, female, gene, gene expression, gene frequency, gene identification, gene linkage disequilibrium, genetic association, genome-wide association study, genotype, genotype phenotype correlation, heritability, human, human tissue, KNH3 gene, major clinical study, male, neuropathology |
| الوصف: | 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), pCOURAGE = 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), pCOURAGE+IPDGC = 3.13 × 10-9) and a novel BST1 locus (rs4698412: β(SE)COURAGE+IPDGC = -0.526(0.096), pCOURAGE+IPDGC = 4.41 × 10-8). Discussion ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 00283878 |
| العلاقة: | http://hdl.handle.net/11615/73726Test |
| DOI: | 10.1212/WNL.0000000000200699 |
| الإتاحة: | https://doi.org/10.1212/WNL.0000000000200699Test http://hdl.handle.net/11615/73726Test |
| رقم الانضمام: | edsbas.FF97DC9B |
| قاعدة البيانات: | BASE |
| تدمد: | 00283878 |
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| DOI: | 10.1212/WNL.0000000000200699 |