Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2011 Jun;7(6):e1002142.
doi: 10.1371/journal.pgen.1002142. Epub 2011 Jun 30.

A two-stage meta-analysis identifies several new loci for Parkinson's disease

International Parkinson's Disease Genomics Consortium (IPDGC); Wellcome Trust Case Control Consortium 2 (WTCCC2)
Collaborators
Meta-Analysis

A two-stage meta-analysis identifies several new loci for Parkinson's disease

International Parkinson's Disease Genomics Consortium (IPDGC) et al. PLoS Genet. 2011 Jun.

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Forest plots detailing effect estimates from the combined analysis of all data contributed by the International Parkinson Disease Genomics Consortium (joint estimates describing constituent effects of Stage 1+Stage 2).
See this image and copyright information in PMC

Similar articles

  • Analysis of GWAS-linked loci in Parkinson disease reaffirms PARK16 as a susceptibility locus.
    Tan EK, Kwok HH, Tan LC, Zhao WT, Prakash KM, Au WL, Pavanni R, Ng YY, Satake W, Zhao Y, Toda T, Liu JJ. Tan EK, et al. Neurology. 2010 Aug 10;75(6):508-12. doi: 10.1212/WNL.0b013e3181eccfcd. Neurology. 2010. PMID: 20697102 Free PMC article.
  • Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies.
    International Parkinson Disease Genomics Consortium; Nalls MA, Plagnol V, Hernandez DG, Sharma M, Sheerin UM, Saad M, Simón-Sánchez J, Schulte C, Lesage S, Sveinbjörnsdóttir S, Stefánsson K, Martinez M, Hardy J, Heutink P, Brice A, Gasser T, Singleton AB, Wood NW. International Parkinson Disease Genomics Consortium, et al. Lancet. 2011 Feb 19;377(9766):641-9. doi: 10.1016/S0140-6736(10)62345-8. Epub 2011 Feb 1. Lancet. 2011. PMID: 21292315 Free PMC article.
  • Genome-wide association study of Parkinson's disease in East Asians.
    Foo JN, Tan LC, Irwan ID, Au WL, Low HQ, Prakash KM, Ahmad-Annuar A, Bei J, Chan AY, Chen CM, Chen YC, Chung SJ, Deng H, Lim SY, Mok V, Pang H, Pei Z, Peng R, Shang HF, Song K, Tan AH, Wu YR, Aung T, Cheng CY, Chew FT, Chew SH, Chong SA, Ebstein RP, Lee J, Saw SM, Seow A, Subramaniam M, Tai ES, Vithana EN, Wong TY, Heng KK, Meah WY, Khor CC, Liu H, Zhang F, Liu J, Tan EK. Foo JN, et al. Hum Mol Genet. 2017 Jan 1;26(1):226-232. doi: 10.1093/hmg/ddw379. Hum Mol Genet. 2017. PMID: 28011712
  • Genetic comorbidities in Parkinson's disease.
    Nalls MA, Saad M, Noyce AJ, Keller MF, Schrag A, Bestwick JP, Traynor BJ, Gibbs JR, Hernandez DG, Cookson MR, Morris HR, Williams N, Gasser T, Heutink P, Wood N, Hardy J, Martinez M, Singleton AB; International Parkinson's Disease Genomics Consortium (IPDGC); Wellcome Trust Case Control Consortium 2 (WTCCC2); North American Brain Expression Consortium (NABEC); United Kingdom Brain Expression Consortium (UKBEC). Nalls MA, et al. Hum Mol Genet. 2014 Feb 1;23(3):831-41. doi: 10.1093/hmg/ddt465. Epub 2013 Sep 20. Hum Mol Genet. 2014. PMID: 24057672 Free PMC article.
  • Genetic variants in sporadic Parkinson's disease: East vs West.
    Peeraully T, Tan EK. Peeraully T, et al. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S63-5. doi: 10.1016/S1353-8020(11)70021-9. Parkinsonism Relat Disord. 2012. PMID: 22166457 Review.
See all similar articles

Cited by

  • Roles of FGF20 in dopaminergic neurons and Parkinson's disease.
    Itoh N, Ohta H. Itoh N, et al. Front Mol Neurosci. 2013 May 31;6:15. doi: 10.3389/fnmol.2013.00015. eCollection 2013. Front Mol Neurosci. 2013. PMID: 23754977 Free PMC article.
  • Fine mapping and resequencing of the PARK16 locus in Parkinson's disease.
    Pihlstrøm L, Rengmark A, Bjørnarå KA, Dizdar N, Fardell C, Forsgren L, Holmberg B, Larsen JP, Linder J, Nissbrandt H, Tysnes OB, Dietrichs E, Toft M. Pihlstrøm L, et al. J Hum Genet. 2015 Jul;60(7):357-62. doi: 10.1038/jhg.2015.34. Epub 2015 Apr 9. J Hum Genet. 2015. PMID: 25855069
  • PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease.
    Beecham GW, Dickson DW, Scott WK, Martin ER, Schellenberg G, Nuytemans K, Larson EB, Buxbaum JD, Trojanowski JQ, Van Deerlin VM, Hurtig HI, Mash DC, Beach TG, Troncoso JC, Pletnikova O, Frosch MP, Ghetti B, Foroud TM, Honig LS, Marder K, Vonsattel JP, Goldman SM, Vinters HV, Ross OA, Wszolek ZK, Wang L, Dykxhoorn DM, Pericak-Vance MA, Montine TJ, Leverenz JB, Dawson TM, Vance JM. Beecham GW, et al. Neurology. 2015 Mar 10;84(10):972-80. doi: 10.1212/WNL.0000000000001332. Epub 2015 Feb 6. Neurology. 2015. PMID: 25663231 Free PMC article.
  • Genetics and epigenetics of Parkinson's disease.
    Coppedè F. Coppedè F. ScientificWorldJournal. 2012;2012:489830. doi: 10.1100/2012/489830. Epub 2012 May 1. ScientificWorldJournal. 2012. PMID: 22623900 Free PMC article.
  • Parkinson disease loci in the mid-western Amish.
    Davis MF, Cummings AC, D'Aoust LN, Jiang L, Velez Edwards DR, Laux R, Reinhart-Mercer L, Fuzzell D, Scott WK, Pericak-Vance MA, Lee SL, Haines JL. Davis MF, et al. Hum Genet. 2013 Nov;132(11):1213-21. doi: 10.1007/s00439-013-1316-1. Epub 2013 Jun 21. Hum Genet. 2013. PMID: 23793441 Free PMC article.
See all "Cited by" articles

References

    1. Zimprich A, Müller-Myhsok B, Farrer M, Leitner P, Sharma M, et al. The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval. American journal of human genetics. 2004;74:11–19. - PMC - PubMed
    1. Paisán-Ruíz C, Jain S, Evans W, Gilks W, Simón J, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron. 2004;44:595–600. - PubMed
    1. Valente EM, Abou-Sleiman P, Caputo V, Muqit M, Harvey K, et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004;304:1158–1160. - PubMed
    1. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997;276:2045–2047. - PubMed
    1. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392:605–608. - PubMed

Publication types

Grants and funding