Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database.
More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published s...
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Public Library of Science (PLoS)
2012
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oai:doaj.org-article:cfc8c07e05884d89b6a183d737c73b812021-11-18T06:18:48ZComprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database.1553-73901553-740410.1371/journal.pgen.1002548https://doaj.org/article/cfc8c07e05884d89b6a183d737c73b812012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22438815/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of -27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P < 5 × 10(-8)) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P = 1.3 × 10(-8)). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.Christina M LillJohannes T RoehrMatthew B McQueenFotini K KavvouraSachin BagadeBrit-Maren M SchjeideLeif M SchjeideEsther MeissnerUte ZauftNicole C AllenTian LiuMarcel SchillingKari J AndersonGary BeechamDaniela BergJoanna M BiernackaAlexis BriceAnita L DeStefanoChuong B DoNicholas ErikssonStewart A FactorMatthew J FarrerTatiana ForoudThomas GasserTaye HamzaJohn A HardyPeter HeutinkErin M Hill-BurnsChristine KleinJeanne C LatourelleDemetrius M MaraganoreEden R MartinMaria MartinezRichard H MyersMichael A NallsNathan PankratzHaydeh PayamiWataru SatakeWilliam K ScottManu SharmaAndrew B SingletonKari StefanssonTatsushi TodaJoyce Y TungJeffery VanceNick W WoodCyrus P Zabetian23andMe Genetic Epidemiology of Parkinson's Disease ConsortiumInternational Parkinson's Disease Genomics ConsortiumParkinson's Disease GWAS ConsortiumWellcome Trust Case Control Consortium 2)Peter YoungRudolph E TanziMuin J KhouryFrauke ZippHans LehrachJohn P A IoannidisLars BertramPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 8, Iss 3, p e1002548 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 Christina M Lill Johannes T Roehr Matthew B McQueen Fotini K Kavvoura Sachin Bagade Brit-Maren M Schjeide Leif M Schjeide Esther Meissner Ute Zauft Nicole C Allen Tian Liu Marcel Schilling Kari J Anderson Gary Beecham Daniela Berg Joanna M Biernacka Alexis Brice Anita L DeStefano Chuong B Do Nicholas Eriksson Stewart A Factor Matthew J Farrer Tatiana Foroud Thomas Gasser Taye Hamza John A Hardy Peter Heutink Erin M Hill-Burns Christine Klein Jeanne C Latourelle Demetrius M Maraganore Eden R Martin Maria Martinez Richard H Myers Michael A Nalls Nathan Pankratz Haydeh Payami Wataru Satake William K Scott Manu Sharma Andrew B Singleton Kari Stefansson Tatsushi Toda Joyce Y Tung Jeffery Vance Nick W Wood Cyrus P Zabetian 23andMe Genetic Epidemiology of Parkinson's Disease Consortium International Parkinson's Disease Genomics Consortium Parkinson's Disease GWAS Consortium Wellcome Trust Case Control Consortium 2) Peter Young Rudolph E Tanzi Muin J Khoury Frauke Zipp Hans Lehrach John P A Ioannidis Lars Bertram Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database. |
| description |
More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of -27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P < 5 × 10(-8)) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P = 1.3 × 10(-8)). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies. |
| format |
article |
| author |
Christina M Lill Johannes T Roehr Matthew B McQueen Fotini K Kavvoura Sachin Bagade Brit-Maren M Schjeide Leif M Schjeide Esther Meissner Ute Zauft Nicole C Allen Tian Liu Marcel Schilling Kari J Anderson Gary Beecham Daniela Berg Joanna M Biernacka Alexis Brice Anita L DeStefano Chuong B Do Nicholas Eriksson Stewart A Factor Matthew J Farrer Tatiana Foroud Thomas Gasser Taye Hamza John A Hardy Peter Heutink Erin M Hill-Burns Christine Klein Jeanne C Latourelle Demetrius M Maraganore Eden R Martin Maria Martinez Richard H Myers Michael A Nalls Nathan Pankratz Haydeh Payami Wataru Satake William K Scott Manu Sharma Andrew B Singleton Kari Stefansson Tatsushi Toda Joyce Y Tung Jeffery Vance Nick W Wood Cyrus P Zabetian 23andMe Genetic Epidemiology of Parkinson's Disease Consortium International Parkinson's Disease Genomics Consortium Parkinson's Disease GWAS Consortium Wellcome Trust Case Control Consortium 2) Peter Young Rudolph E Tanzi Muin J Khoury Frauke Zipp Hans Lehrach John P A Ioannidis Lars Bertram |
| author_facet |
Christina M Lill Johannes T Roehr Matthew B McQueen Fotini K Kavvoura Sachin Bagade Brit-Maren M Schjeide Leif M Schjeide Esther Meissner Ute Zauft Nicole C Allen Tian Liu Marcel Schilling Kari J Anderson Gary Beecham Daniela Berg Joanna M Biernacka Alexis Brice Anita L DeStefano Chuong B Do Nicholas Eriksson Stewart A Factor Matthew J Farrer Tatiana Foroud Thomas Gasser Taye Hamza John A Hardy Peter Heutink Erin M Hill-Burns Christine Klein Jeanne C Latourelle Demetrius M Maraganore Eden R Martin Maria Martinez Richard H Myers Michael A Nalls Nathan Pankratz Haydeh Payami Wataru Satake William K Scott Manu Sharma Andrew B Singleton Kari Stefansson Tatsushi Toda Joyce Y Tung Jeffery Vance Nick W Wood Cyrus P Zabetian 23andMe Genetic Epidemiology of Parkinson's Disease Consortium International Parkinson's Disease Genomics Consortium Parkinson's Disease GWAS Consortium Wellcome Trust Case Control Consortium 2) Peter Young Rudolph E Tanzi Muin J Khoury Frauke Zipp Hans Lehrach John P A Ioannidis Lars Bertram |
| author_sort |
Christina M Lill |
| title |
Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database. |
| title_short |
Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database. |
| title_full |
Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database. |
| title_fullStr |
Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database. |
| title_full_unstemmed |
Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database. |
| title_sort |
comprehensive research synopsis and systematic meta-analyses in parkinson's disease genetics: the pdgene database. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/cfc8c07e05884d89b6a183d737c73b81 |
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