Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

International Parkinson's Disease Genomics Consortium (IPDGC), Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI), 23andMe, GenePD, NeuroGenetics Research Consortium (NGRC), Hussman Institute of Human Genomics (HIHG), The Ashkenazi Jewish Dataset Investigator, Cohorts 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 Consortium, Alzheimer Genetic Analysis Group

Research output: Contribution to journalArticle

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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<sup>-16</sup>). We also show six risk loci associated with proximal gene expression or DNA methylation.

Original languageEnglish
Pages (from-to)989-993
Number of pages5
JournalNature Genetics
Volume46
Issue number9
DOIs
StatePublished - 2014

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Parkinson Disease
Meta-Analysis
Genome
Odds Ratio
Genome-Wide Association Study
DNA Methylation
Single Nucleotide Polymorphism
Confidence Intervals
Gene Expression

ASJC Scopus subject areas

  • Genetics

Cite this

International Parkinson's Disease Genomics Consortium (IPDGC), Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI), 23andMe, GenePD, NeuroGenetics Research Consortium (NGRC), Hussman Institute of Human Genomics (HIHG), ... Alzheimer Genetic Analysis Group (2014). Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nature Genetics, 46(9), 989-993. https://doi.org/10.1038/ng.3043

Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. / International Parkinson's Disease Genomics Consortium (IPDGC); Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI); 23andMe; GenePD; NeuroGenetics Research Consortium (NGRC); Hussman Institute of Human Genomics (HIHG); The Ashkenazi Jewish Dataset Investigator; Cohorts 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 Consortium; Alzheimer Genetic Analysis Group.

In: Nature Genetics, Vol. 46, No. 9, 2014, p. 989-993.

Research output: Contribution to journalArticle

International Parkinson's Disease Genomics Consortium (IPDGC), Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI), 23andMe, GenePD, NeuroGenetics Research Consortium (NGRC), Hussman Institute of Human Genomics (HIHG), The Ashkenazi Jewish Dataset Investigator, Cohorts 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 Consortium & Alzheimer Genetic Analysis Group 2014, 'Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease', Nature Genetics, vol. 46, no. 9, pp. 989-993. https://doi.org/10.1038/ng.3043
International Parkinson's Disease Genomics Consortium (IPDGC), Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI), 23andMe, GenePD, NeuroGenetics Research Consortium (NGRC), Hussman Institute of Human Genomics (HIHG) et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nature Genetics. 2014;46(9):989-993. https://doi.org/10.1038/ng.3043
International Parkinson's Disease Genomics Consortium (IPDGC) ; Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI) ; 23andMe ; GenePD ; NeuroGenetics Research Consortium (NGRC) ; Hussman Institute of Human Genomics (HIHG) ; The Ashkenazi Jewish Dataset Investigator ; Cohorts 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 Consortium ; Alzheimer Genetic Analysis Group. / Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. In: Nature Genetics. 2014 ; Vol. 46, No. 9. pp. 989-993.
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AU - Arepalli, Sampath

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AU - Stefansson, Hreinn

AU - Liu, Xinmin

AU - Pliner, Hannah

AU - Lee, Joseph H.

AU - Cheng, Rong

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AU - Ioannidis, John P A

AU - Hadjigeorgiou, Georgios M.

AU - Bis, Joshua C.

AU - Martinez, Maria

AU - Perlmutter, Joel S.

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