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. 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
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Free PMC article

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


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


The authors declare no competing financial interests.


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.

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