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A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

English version České info

A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5×10−10, PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci.

Vyšlo v časopise: A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease. PLoS Genet 7(6): e32767. doi:10.1371/journal.pgen.1002142
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002142

Souhrn

A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5×10−10, PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci.

Zdroje

1. ZimprichAMüller-MyhsokBFarrerMLeitnerPSharmaM 2004 The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval. American journal of human genetics 74 11 19

2. Paisán-RuízCJainSEvansWGilksWSimónJ 2004 Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44 595 600

3. ValenteEMAbou-SleimanPCaputoVMuqitMHarveyK 2004 Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304 1158 1160

4. PolymeropoulosMHLavedanCLeroyEIdeSEDehejiaA 1997 Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276 2045 2047

5. KitadaTAsakawaSHattoriNMatsumineHYamamuraY 1998 Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392 605 608

6. BonifatiVRizzuPvan BarenMSchaapOBreedveldG 2003 Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299 256 259

7. Simón-SánchezJSchulteCBrasJSharmaMGibbsR 2009 Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nature Genetics 41 1308 1312

8. SatakeWNakabayashiYMizutaIHirotaYItoC 2009 Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nature Genetics 41 1303 1307

9. SaadMLesageSSaint-PierreACorvolJ-CZelenikaD 2011 Genome-wide association study confirms BST1 and suggests a locus on 12q24 as risk loci for Parkinson's disease in the European population. Human Molecular Genetics 20 615 627

10. Simon-SanchezJvan HiltenJvan de WarrenburgBPostBBerendseH 2011 Genome-wide association study confirms extant PD risk loci among the Dutch. European Journal of Human Genetics aop

11. 2011 Dissection of the genetics of Parkinson's disease identifies an additional association 5′ of SNCA and multiple associated haplotypes at 17q21. Human Molecular Genetics 20 345 353

12. PankratzNWilkJLatourelleJDeStefanoAHalterC 2009 Genomewide association study for susceptibility genes contributing to familial Parkinson disease. Human genetics 124 593 605

13. HamzaTZabetianCTenesaALaederachAMontimurroJ 2010 Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease. Nature Genetics 42 781 785

14. LiYWillerCDingJScheetPAbecasisG 2010 MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genetic epidemiology 34 816 834

15. NallsMPlagnolVHernandezDSharmaMSheerinU-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

16. van der WaltJNoureddineMKittappaRHauserMScottW 2004 Fibroblast growth factor 20 polymorphisms and haplotypes strongly influence risk of Parkinson disease. American journal of human genetics 74 1121 1127

17. SmirnovaTStinnakreJMalletJ 1993 Characterization of a presynaptic glutamate receptor. Science 262 430 433

18. WangGvan der WaltJMayhewGLiY-JZüchnerS 2008 Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein. American journal of human genetics 82 283 289

19. WiderCDachselJSotoAHeckmanMDiehlN 2009 FGF20 and Parkinson's disease: no evidence of association or pathogenicity via alpha-synuclein expression. Movement disorders 24 455 459

20. GilksWAbou-SleimanPGandhiSJainSSingletonA 2005 A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet 365 415 416

21. ZollnerSPritchardJ 2007 Overcoming the winner's curse: estimating penetrance parameters from case-control data. American journal of human genetics 80 605 615

22. PlagnolVSmythDToddJClaytonD 2008 Statistical independence of the colocalized association signals for type 1 diabetes and RPS26 gene expression on chromosome 12q13. Biostatistics (Oxford, England)

23. ShimizuFKatagiriTSuzukiMWatanabeTKOkunoS 1997 Cloning and chromosome assignment to 1q32 of a human cDNA (RAB7L1) encoding a small GTP-binding protein, a member of the RAS superfamily. Cytogenetics and cell genetics 77 261 263

24. KoshimuraKOhueTAkiyamaYItohAMiwaS 1992 L-dopa administration enhances exocytotic dopamine release in vivo in the rat striatum. Life sciences 51 747 755

25. CabinDShimazuKMurphyDColeNGottschalkW 2002 Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. The Journal of neuroscience 22 8797 8807

26. GrundtKHagaIVAleporou-MarinouVDrososYWanvikB 2004 Characterisation of the NUCKS gene on human chromosome 1q32.1 and the presence of a homologous gene in different species. Biochemical and biophysical research communications 323 796 801

27. HeltonTOtsukaTLeeM-CMuYEhlersM 2008 Pruning and loss of excitatory synapses by the parkin ubiquitin ligase. Proceedings of the National Academy of Sciences of the United States of America 105 19492 19497

28. ClarimonJXiromerisiouGEerolaJGourbaliVHellströmO 2005 Lack of evidence for a genetic association between FGF20 and Parkinson's disease in Finnish and Greek patients. BMC neurology 5

29. JeffersMShimketsRPrayagaSBoldogFYangM 2001 Identification of a novel human fibroblast growth factor and characterization of its role in oncogenesis. Cancer research 61 3131 3138

30. OhmachiSMikamiTKonishiMMiyakeAItohN 2003 Preferential neurotrophic activity of fibroblast growth factor-20 for dopaminergic neurons through fibroblast growth factor receptor-1c. J Neurosci Res 72 436 443

31. TucciANallsMHouldenHReveszTSingletonA 2010 Genetic variability at the PARK16 locus. European journal of human genetics : EJHG 18 1356 1359

32. DicksonSWangKKrantzIHakonarsonHGoldsteinD 2010 Rare Variants Create Synthetic Genome-Wide Associations. PLoS Biol 8 e1000294 doi:10.1371/journal.pbio.1000294

33. PurcellSNealeBTodd-BrownKThomasLFerreiraM 2007 PLINK: a tool set for whole-genome association and population-based linkage analyses. American journal of human genetics 81 559 575

34. PriceAPattersonNPlengeRWeinblattMShadickN 2006 Principal components analysis corrects for stratification in genome-wide association studies. Nature Genetics 38 904 909

35. 2010 A map of human genome variation from population-scale sequencing. Nature 467 1061 1073

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