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 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 Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls.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.
Vyšlo v časopise:
Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database. PLoS Genet 8(3): e32767. doi:10.1371/journal.pgen.1002548
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002548
Souhrn
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.
Zdroje
1. de LauLMLBretelerMMB 2006 Epidemiology of Parkinson's disease. Lancet Neurol 5 525 535 doi:10.1016/S1474-4422(06)70471-9
2. HardyJLewisPReveszTLeesAPaisan-RuizC 2009 The genetics of Parkinson's syndromes: a critical review. Curr Opin Genet Dev 19 254 265 doi:10.1016/j.gde.2009.03.008
3. Vilariño-GüellCWiderCRossOADachselJCKachergusJM 2011 VPS35 mutations in Parkinson disease. Am J Hum Genet 89 162 167 doi:10.1016/j.ajhg.2011.06.001
4. ZimprichABenet-PagèsAStruhalWGrafEEckSH 2011 A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am J Hum Genet 89 168 175 doi:10.1016/j.ajhg.2011.06.008
5. Chartier-HarlinM-CDachselJCVilariño-GüellCLincolnSJLeprêtreF 2011 Translation initiator EIF4G1 mutations in familial Parkinson disease. Am J Hum Genet 89 398 406 doi:10.1016/j.ajhg.2011.08.009
6. MaraganoreDMde AndradeMElbazAFarrerMJIoannidisJP 2006 Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease. JAMA 296 661 670 doi:10.1001/jama.296.6.661
7. ZabetianCPYamamotoMLopezANUjikeHMataIF 2009 LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease. Mov Disord 24 1034 1041 doi:10.1002/mds.22514
8. GorisAWilliams-GrayCHClarkGRFoltynieTLewisSJG 2007 Tau and alpha-synuclein in susceptibility to, and dementia in, Parkinson's disease. Ann Neurol 62 145 153 doi:10.1002/ana.21192
9. SidranskyENallsMAAaslyJOAharon-PeretzJAnnesiG 2009 Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med 361 1651 1661 doi:10.1056/NEJMoa0901281
10. MaraganoreDMde AndradeMLesnickTGStrainKJFarrerMJ 2005 High-resolution whole-genome association study of Parkinson disease. Am J Hum Genet 77 685 693 doi:10.1086/496902
11. FungH-CScholzSMatarinMSimón-SánchezJHernandezD 2006 Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data. Lancet Neurol 5 911 916 doi:10.1016/S1474-4422(06)70578-6
12. PankratzNWilkJBLatourelleJCDeStefanoALHalterC 2009 Genomewide association study for susceptibility genes contributing to familial Parkinson disease. Hum Genet 124 593 605 doi:10.1007/s00439-008-0582-9
13. Simón-SánchezJSchulteCBrasJMSharmaMGibbsJR 2009 Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat Genet 41 1308 1312 doi:10.1038/ng.487
14. SatakeWNakabayashiYMizutaIHirotaYItoC 2009 Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat Genet 41 1303 1307 doi:10.1038/ng.485
15. EdwardsTLScottWKAlmonteCBurtAPowellEH 2010 Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease. Ann Hum Genet 74 97 109 doi:10.1111/j.1469-1809.2009.00560.x
16. HamzaTHZabetianCPTenesaALaederachAMontimurroJ 2010 Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease. Nat Genet 42 781 785 doi:10.1038/ng.642
17. SpencerCCAPlagnolVStrangeAGardnerMPaisan-RuizC 2011 Dissection of the genetics of Parkinson's disease identifies an additional association 5′ of SNCA and multiple associated haplotypes at 17q21. Hum Mol Genet 20 345 353 doi:10.1093/hmg/ddq469
18. SaadMLesageSSaint-PierreACorvolJ-CZelenikaD 2011 Genome-wide association study confirms BST1 and suggests a locus on 12q24 as the risk loci for Parkinson's disease in the European population. Hum Mol Genet 20 615 627 doi:10.1093/hmg/ddq497
19. Simón-SánchezJvan HiltenJJvan de WarrenburgBPostBBerendseHW 2011 Genome-wide association study confirms extant PD risk loci among the Dutch. Eur J Hum Genet 19 655 661 doi:10.1038/ejhg.2010.254
20. EvangelouEMaraganoreDMIoannidisJPA 2007 Meta-analysis in genome-wide association datasets: strategies and application in Parkinson disease. PLoS ONE 2 e196 doi:10.1371/journal.pone.0000196
21. NallsMAPlagnolVHernandezDGSharmaMSheerinU-M 2011 Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet 377 641 649 doi:10.1016/S0140-6736(10)62345-8
22. DoCBTungJYDorfmanEKieferAKDrabantEM 2011 Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson's disease. PLoS Genet 7 e1002141 doi:10.1371/journal.pgen.1002141
23. SharmaMIoannidisJPAAaslyJOAnnesiGBriceA n.d. Large-scale replication and heterogeneity in Parkinson disease genetic loci. Neurology in press
24. LinD-YSullivanPF 2009 Meta-analysis of genome-wide association studies with overlapping subjects. Am J Hum Genet 85 862 872 doi:10.1016/j.ajhg.2009.11.001
25. IoannidisJPA 2008 Effect of formal statistical significance on the credibility of observational associations. Am J Epidemiol 168 374 383; discussion 384–390 doi:10.1093/aje/kwn156
26. IoannidisJPABoffettaPLittleJO'BrienTRUitterlindenAG 2008 Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol 37 120 132 doi:10.1093/ije/dym159
27. KhouryMJBertramLBoffettaPButterworthASChanockSJ 2009 Genome-wide association studies, field synopses, and the development of the knowledge base on genetic variation and human diseases. Am J Epidemiol 170 269 279 doi:10.1093/aje/kwp119
28. KentWJZweigASBarberGHinrichsASKarolchikD 2010 BigWig and BigBed: enabling browsing of large distributed datasets. Bioinformatics 26 2204 2207 doi:10.1093/bioinformatics/btq351
29. MyersAJGibbsJRWebsterJARohrerKZhaoA 2007 A survey of genetic human cortical gene expression. Nat Genet 39 1494 1499 doi:10.1038/ng.2007.16
30. Varnum-FinneyBVenstromKMullerUKyptaRBackusC 1995 The integrin receptor alpha 8 beta 1 mediates interactions of embryonic chick motor and sensory neurons with tenascin-C. Neuron 14 1213 1222
31. DerSimonianRLairdN 1986 Meta-analysis in clinical trials. Control Clin Trials 7 177 188
32. HarbordRMEggerMSterneJAC 2006 A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med 25 3443 3457 doi:10.1002/sim.2380
33. BertramLMcQueenMBMullinKBlackerDTanziRE 2007 Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 39 17 23 doi:10.1038/ng1934
34. AllenNCBagadeSMcQueenMBIoannidisJPAKavvouraFK 2008 Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat Genet 40 827 834 doi:10.1038/ng.171
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2012 Číslo 3
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- PIF4–Mediated Activation of Expression Integrates Temperature into the Auxin Pathway in Regulating Hypocotyl Growth
- Metabolic Profiling of a Mapping Population Exposes New Insights in the Regulation of Seed Metabolism and Seed, Fruit, and Plant Relations
- Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database
- Networks of Neuronal Genes Affected by Common and Rare Variants in Autism Spectrum Disorders