Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2014 Sep;46(9):989-93.
doi: 10.1038/ng.3043. Epub 2014 Jul 27.

Large-scale Meta-Analysis of Genome-Wide Association Data Identifies Six New Risk Loci for Parkinson's Disease

Mike A Nalls  1 Nathan Pankratz  2 Christina M Lill  3 Chuong B Do  4 Dena G Hernandez  5 Mohamad Saad  6 Anita L DeStefano  7 Eleanna Kara  8 Jose Bras  8 Manu Sharma  9 Claudia Schulte  10 Margaux F Keller  11 Sampath Arepalli  11 Christopher Letson  11 Connor Edsall  11 Hreinn Stefansson  12 Xinmin Liu  13 Hannah Pliner  11 Joseph H Lee  14 Rong Cheng  14 International Parkinson's Disease Genomics Consortium (IPDGC)Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI)23andMeGenePDNeuroGenetics Research Consortium (NGRC)Hussman Institute of Human Genomics (HIHG)Ashkenazi Jewish Dataset InvestigatorCohorts for Health and Aging Research in Genetic Epidemiology (CHARGE)North American Brain Expression Consortium (NABEC)United Kingdom Brain Expression Consortium (UKBEC)Greek Parkinson's Disease ConsortiumAlzheimer Genetic Analysis GroupM Arfan Ikram  15 John P A Ioannidis  16 Georgios M Hadjigeorgiou  17 Joshua C Bis  18 Maria Martinez  19 Joel S Perlmutter  20 Alison Goate  21 Karen Marder  22 Brian Fiske  23 Margaret Sutherland  24 Georgia Xiromerisiou  25 Richard H Myers  26 Lorraine N Clark  27 Kari Stefansson  12 John A Hardy  28 Peter Heutink  29 Honglei Chen  30 Nicholas W Wood  8 Henry Houlden  8 Haydeh Payami  31 Alexis Brice  32 William K Scott  33 Thomas Gasser  10 Lars Bertram  34 Nicholas Eriksson  4 Tatiana Foroud  35 Andrew B Singleton  11
Collaborators, Affiliations
Free PMC article
Meta-Analysis

Large-scale Meta-Analysis of Genome-Wide Association Data Identifies Six New Risk Loci for Parkinson's Disease

Mike A Nalls et al. Nat Genet. .
Free PMC article

Abstract

We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.

Conflict of interest statement

COMPETING FINANCIAL INTERESTS

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Manhattan plot of discovery phase meta-analyses.
Figure 2
Figure 2
Forest plots describing cohort level and summary effects of risk profile analyses.

Similar articles

See all similar articles

Cited by 546 articles

See all "Cited by" articles

References

    1. Lill CM, et al. Comprehensive research synopsis and systematic meta-analyses in Parkinson’s disease genetics: The PDGene database. PLoS Genet. 2012;8:e1002548. - PMC - PubMed
    1. Do CB, et al. Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson’s disease. PLoS Genet. 2011;7:e1002141. - PMC - PubMed
    1. International Parkinson Disease Genomics Consortium et al. Imputation of sequence variants for identification of genetic risks for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet. 2011;377:641–9. - PMC - PubMed
    1. International Parkinson’s Disease Genomics Consortium (IPDGC) & Wellcome Trust Case Control Consortium 2 (WTCCC2) A two-stage meta-analysis identifies several new loci for Parkinson’s disease. PLoS Genet. 2011;7:e1002142. - PMC - PubMed
    1. Edwards TL, et al. Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease. Ann Hum Genet. 2010;74:97–109. - PMC - PubMed

Publication types

Grant support

Feedback