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

Mike A Nalls; Nathan Pankratz; Christina M Lill; Chuong B Do; Dena G Hernandez; Mohamad Saad; Anita L DeStefano; Eleanna Kara; Jose Bras; Manu Sharma; Claudia Schulte; Margaux F Keller; Sampath Arepalli; Christopher Letson; Connor Edsall; Hreinn Stefansson; Xinmin Liu; Hannah Pliner; Joseph H Lee; Rong Cheng; M Arfan Ikram; John P A Ioannidis; Georgios M Hadjigeorgiou; Joshua C Bis; Maria Martinez; Joel S Perlmutter; Alison Goate; Karen Marder; Brian Fiske; Margaret Sutherland; Georgia Xiromerisiou; Richard H Myers; Lorraine N Clark; Kari Stefansson; John A Hardy; Peter Heutink; Honglei Chen; Nicholas W Wood; Henry Houlden; Haydeh Payami; Alexis Brice; William K Scott; Thomas Gasser; Lars Bertram; Nicholas Eriksson; Tatiana Foroud; Andrew B Singleton; Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI); Panos Deloukas

doi:10.1038/ng.3043

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

Journal article

Peer reviewed

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

Mike A Nalls, Nathan Pankratz, Christina M Lill, Chuong B Do, Dena G Hernandez, Mohamad Saad, Anita L DeStefano, Eleanna Kara, Jose Bras, Manu Sharma, …

Nature genetics, Vol.46(9), pp.989-+

01/09/2014

DOI: https://doi.org/10.1038/ng.3043

PMCID: PMC4146673

PMID: 25064009

Abstract

Case-Control Studies

Genetic Loci

Genetic Predisposition to Disease

Genome-Wide Association Study - methods

Genotype

Humans

Parkinson Disease - genetics

Polymorphism, Single Nucleotide

Risk Factors

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.

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Title: Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease
Creators - without role: Mike A Nalls - National Institute on Aging
Nathan Pankratz - University of Minnesota
Christina M Lill - Max Planck Institute for Molecular Genetics
Chuong B Do - 23andMe
Dena G Hernandez - National Institute on Aging
Mohamad Saad - Université Toulouse III - Paul Sabatier
Anita L DeStefano - Boston University
Eleanna Kara - University College London
Jose Bras - University College London
Manu Sharma - University of Tübingen
Claudia Schulte - Hertie Institute for Clinical Brain Research
Margaux F Keller - National Institute on Aging
Sampath Arepalli - National Institute on Aging
Christopher Letson - National Institute on Aging
Connor Edsall - National Institute on Aging
Hreinn Stefansson - deCODE Genetics
Xinmin Liu - Columbia University Irving Medical Center
Hannah Pliner - National Institute on Aging
Joseph H Lee - Columbia University Irving Medical Center
Rong Cheng - Columbia University Irving Medical Center
M Arfan Ikram - Erasmus MC
John P A Ioannidis - Stanford University
Georgios M Hadjigeorgiou - University of Thessaly
Joshua C Bis - University of Washington
Maria Martinez - Inserm
Joel S Perlmutter - Hope Center for Neurological Disorders
Alison Goate - Hope Center for Neurological Disorders
Karen Marder - Columbia University Irving Medical Center
Brian Fiske - Michael J. Fox Foundation
Margaret Sutherland - National Institute of Neurological Disorders and Stroke
Georgia Xiromerisiou - University of Thessaly
Richard H Myers - Boston University School of Medicine
Lorraine N Clark - Columbia University Irving Medical Center
Kari Stefansson - deCODE Genetics
John A Hardy - University College London
Peter Heutink - German Center for Neurodegenerative Diseases
Honglei Chen - National Institute of Environmental Health Sciences
Nicholas W Wood - University College London
Henry Houlden - University College London
Haydeh Payami - New York State Department of Health
Alexis Brice - Inserm
William K Scott - University of Miami
Thomas Gasser - Hertie Institute for Clinical Brain Research
Lars Bertram - Max Planck Institute for Molecular Genetics
Nicholas Eriksson - 23andMe
Tatiana Foroud - Indiana University
Andrew B Singleton - National Institute on Aging
Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI)
Panos Deloukas - King Abdulaziz University
Publication Details: Nature genetics, Vol.46(9), pp.989-+
Grant note: 083948/Z/07/Z / Wellcome Trust G1001253 / Medical Research Council G0802760 / Medical Research Council AG033193 / NIA NIH HHS MR/L016400/1 / Medical Research Council K02 NS073836 / NINDS NIH HHS MR/L010305/1 / Medical Research Council 1K23NS070867 / NINDS NIH HHS R01 NS075321 / NINDS NIH HHS G-0909 / Parkinson's UK P50NS071674 / NINDS NIH HHS NS060113 / NINDS NIH HHS U01 NS082151 / NINDS NIH HHS G1100479 / Medical Research Council Z01 AG000949-03 / Intramural NIH HHS Z01 AG000932-01 / Intramural NIH HHS MC_PC_09003 / Medical Research Council G0901254 / Medical Research Council AG025259 / NIA NIH HHS R01 AG041797 / NIA NIH HHS G0701075 / Medical Research Council G0700943 / Medical Research Council R01-NS-36960 / NINDS NIH HHS G0802462 / Medical Research Council NS050487 / NINDS NIH HHS 076113 / Wellcome Trust G1100643 / Medical Research Council MC_G0901330 / Medical Research Council P50 NS071674 / NINDS NIH HHS 2UL1 RR024156 / NCRR NIH HHS 1KL2RR024154 / NCRR NIH HHS 085475 / Wellcome Trust MR/L501554/1 / Medical Research Council R44 HG006981 / NHGRI NIH HHS R01 NS076843 / NINDS NIH HHS R01CA141668 / NCI NIH HHS G-0907 / Parkinson's UK R01 HL120393 / NHLBI NIH HHS NS036630 / NINDS NIH HHS R01NS037167 / NINDS NIH HHS AG031287 / NIA NIH HHS P30AG024826 / NIA NIH HHS F-1202 / Parkinson's UK AG16495 / NIA NIH HHS AG08122 / NIA NIH HHS P30AG013846 / NIA NIH HHS UL1 TR001108 / NCATS NIH HHS UL1 TR000124 / NCATS NIH HHS NS17950 / NINDS NIH HHS WT089698/Z/09/Z / Wellcome Trust G108/638 / Medical Research Council R01 NS088538 / NINDS NIH HHS J-0804 / Parkinson's UK MR/J004758/1 / Medical Research Council U24 AG056270 / NIA NIH HHS UL1TR000124 / NCATS NIH HHS U24 AG021886 / NIA NIH HHS P50 NS038377 / NINDS NIH HHS 090355 / Wellcome Trust MC_G1000735 / Medical Research Council 089698 / Wellcome Trust DK063491 / NIDDK NIH HHS AG023629 / NIA NIH HHS
Identifiers: 9938788608331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article