A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

Vincent Plagnol; Michael A. Nalls; Jose M. Bras; Dena G. Hernandez; Manu Sharma; Una-Marie Sheerin; Mohamad Saad; Javier Simon-Sanchez; Claudia Schulte; Suzanne Lesage; Sigurlaug Sveinbjornsdottir; Philippe Amouyel; Sampath Arepalli; Gavin Band; Roger A. Barker; Celine Bellinguez; Yoav Ben-Shlomo; Henk W. Berendse; Daniela Berg; Kailash Bhatia; Rob M. A. de Bie; Alessandro Biffi; Bas Bloem; Zoltan Bochdanovits; Michael Bonin; Kathrin Brockmann; Janet Brooks; David J. Burn; Gavin Charlesworth; Honglei Chen; Patrick F. Chinnery; Sean Chong; Carl E. Clarke; Mark R. Cookson; J. Mark Cooper; Jean Christophe Corvol; Carl Counsell; Philippe Damier; Jean-Francois Dartigues; Panos Deloukas; Guenther Deuschl; David T. Dexter; Karin D. van Dijk; Allissa Dillman; Frank Durif; Alexandra Duerr; Sarah Edkins; Jonathan R. Evans; Thomas Foltynie; Colin Freeman; Jianjun Gao; Michelle Gardner; J. Raphael Gibbs; Alison Goate; Emma Gray; Rita Guerreiro; Omar Gustafsson; Clare Harris; Garrett Hellenthal; Jacobus J. van Hilten; Albert Hofman; Albert Hollenbeck; Janice Holton; Michele Hu; Xuemei Huang; Heiko Huber; Gavin Hudson; Sarah E. Hunt; Johanna Huttenlocher; Thomas Illig; Palmi V. Jonsson; Cordelia Langford; Andrew Lees; Peter Lichtner; Patricia Limousin; Grisel Lopez; Delia Lorenz; Alisdair McNeill; Catriona Moorby; Matthew Moore; Huw Morris; Karen E. Morrison; Ese Mudanohwo; Sean S. O'Sullivan; Justin Pearson; Richard Pearson; Joel S. Perlmutter; Hjoervar Petursson; Matti Pirinen; Pierre Pollak; Bart Post; Simon Potter; Bernard Ravina; Tamas Revesz; Olaf Riess; Fernando Rivadeneira; Patrizia Rizzu; Mina Ryten; Stephen Sawcer; Anthony Schapira; Hans Scheffer; Karen Shaw; Ira Shoulson; Ellen Sidransky; Rohan de Silva; Colin Smith; Chris C. A. Spencer; Hreinn Stefansson; Stacy Steinberg; Joanna D. Stockton; Amy Strange; Zhan Su; Kevin Talbot; Carlie M. Tanner; Avazeh Tashakkori-Ghanbaria; Francois Tison; Daniah Trabzuni; Bryan J. Traynor; Andre G. Uitterlinden; Jana Vandrovcova; Daan Velseboer; Marie Vidailhet; Damjan Vukcevic; Robert Walker; Bart van de Warrenburg; Michael E. Weale; Mirdhu Wickremaratchi; Nigel Williams; Caroline H. Williams-Gray; Sophie Winder-Rhodes; Kari Stefansson; Maria Martinez; Peter Donnelly; Andrew B. Singleton; John Hardy; Peter Heutink; Alexis Brice; Thomas Gasser; Nicholas W. Wood; WTCCC2

doi:10.1371/journal.pgen.1002142

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A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

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A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

Vincent Plagnol, Michael A. Nalls, Jose M. Bras, Dena G. Hernandez, Manu Sharma, Una-Marie Sheerin, Mohamad Saad, Javier Simon-Sanchez, Claudia Schulte, Suzanne Lesage, …

PLoS genetics, Vol.7(6), pp.e1002142-e1002142

01/06/2011

DOI: https://doi.org/10.1371/journal.pgen.1002142

PMID: 21738488

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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<5x10(-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.

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Title: A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease
Creators - without role: Vincent Plagnol - UCL, UCL Genet Inst, London, England
Michael A. Nalls - NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Jose M. Bras - UCL, Dept Mol Neurosci, Inst Neurol, London, England
Dena G. Hernandez - NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Manu Sharma - Inserm
Una-Marie Sheerin - UCL, Dept Mol Neurosci, Inst Neurol, London, England
Mohamad Saad - Inserm
Javier Simon-Sanchez - University of Amsterdam
Claudia Schulte - University of Tübingen
Suzanne Lesage - Inserm
Sigurlaug Sveinbjornsdottir - Landspitali Univ Hosp, Dept Neurol, Reykjavik, Iceland
Philippe Amouyel - Inserm
Sampath Arepalli - UCL, UCL Genet Inst, London, England
Gavin Band - Wellcome Trust
Roger A. Barker - University of Cambridge
Celine Bellinguez - Wellcome Trust
Yoav Ben-Shlomo - University of Bristol
Henk W. Berendse - University of Amsterdam
Daniela Berg - University of Tübingen
Kailash Bhatia - UCL, Inst Neurol, Dept Motor Neurosci, London, England
Rob M. A. de Bie - University of Amsterdam
Alessandro Biffi - Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA
Bas Bloem - Radboud University Nijmegen
Zoltan Bochdanovits - University of Amsterdam
Michael Bonin - University of Tübingen
Kathrin Brockmann - University of Tübingen
Janet Brooks - UCL, UCL Genet Inst, London, England
David J. Burn - Newcastle Univ, Clin Ageing Res Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Gavin Charlesworth - UCL, Dept Mol Neurosci, Inst Neurol, London, England
Honglei Chen - Triangle
Patrick F. Chinnery - Newcastle University
Sean Chong - NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Carl E. Clarke - University of Birmingham
Mark R. Cookson - NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
J. Mark Cooper - UCL, Inst Neurol, Dept Clin Neurosci, London, England
Jean Christophe Corvol - Inserm
Carl Counsell - University of Aberdeen
Philippe Damier - CHU Nantes, CIC0004, Serv Neurol, F-44035 Nantes 01, France
Jean-Francois Dartigues - Inserm
Panos Deloukas - Wellcome Sanger Institute
Guenther Deuschl - Univ Kiel, Neurol Klin, Univ Klinikum Schleswig Holstein, D-2300 Kiel, Germany
David T. Dexter - University of London
Karin D. van Dijk - University of Amsterdam
Allissa Dillman - NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Frank Durif - Hop Gabriel Montpied, Serv Neurol, Clermont Ferrand, France
Alexandra Duerr - German Ctr Neurodegenerat Dis, Deutsch Zentrum Neurodegenerat Erkrangungen, Tubingen, Germany
Sarah Edkins - Wellcome Sanger Institute
Jonathan R. Evans - University of Cambridge
Thomas Foltynie
Colin Freeman - Wellcome Trust
Jianjun Gao - Triangle
Michelle Gardner - UCL, Dept Mol Neurosci, Inst Neurol, London, England
J. Raphael Gibbs - NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Alison Goate - Supreme Council Of Health
Emma Gray - Wellcome Sanger Institute
Rita Guerreiro - UCL, Dept Mol Neurosci, Inst Neurol, London, England
Omar Gustafsson - 14 DeCODE Genet, Reykjavik, Iceland
Clare Harris - University of Aberdeen
Garrett Hellenthal - Wellcome Trust
Jacobus J. van Hilten - Leiden University
Albert Hofman - College Station Medical Center
Albert Hollenbeck - Amer Assoc Retired Persons, Washington, DC USA
Janice Holton - UCL, Inst Neurol, Queen Sq Brain Bank Neurol Disorders, London, England
Michele Hu - John Radcliffe Hosp, Dept Clin Neurol, Oxford OX3 9DU, England
Xuemei Huang - Pennsylvania State University
Heiko Huber - University of Tübingen
Gavin Hudson - Newcastle Univ, Dept Neurol, Sch Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Sarah E. Hunt - Wellcome Sanger Institute
Johanna Huttenlocher - Inserm
Thomas Illig - Helmholtz Zentrum München
Palmi V. Jonsson - Landspitali Univ Hosp, Dept Geriatr, Reykjavik, Iceland
Cordelia Langford - University of Cambridge
Andrew Lees - UCL, Inst Neurol, Queen Sq Brain Bank Neurol Disorders, London, England
Peter Lichtner - Helmholtz Zentrum München
Patricia Limousin - UCL, Inst Neurol, Sobell Dept, Unit Funct Neurosurg, London, England
Grisel Lopez - College Station Medical Center
Delia Lorenz - Univ Kiel, Neurol Klin, Univ Klinikum Schleswig Holstein, D-2300 Kiel, Germany
Alisdair McNeill - UCL, Inst Neurol, Dept Clin Neurosci, London, England
Catriona Moorby - University of Birmingham
Matthew Moore - NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Huw Morris - Cardiff University
Karen E. Morrison - University of Birmingham
Ese Mudanohwo - UCL, Natl Hosp Neurol & Neurosurg, Inst Neurol, Neurogenet Unit, London, England
Sean S. O'Sullivan - UCL, Inst Neurol, Queen Sq Brain Bank Neurol Disorders, London, England
Justin Pearson - Cardiff University
Richard Pearson - Wellcome Trust
Joel S. Perlmutter - Supreme Council Of Health
Hjoervar Petursson - University of Tübingen
Matti Pirinen - Wellcome Trust
Pierre Pollak - CHU Grenoble, Serv Neurol, F-38043 Grenoble, France
Bart Post - Radboud University Nijmegen
Simon Potter - Wellcome Sanger Institute
Bernard Ravina - Biogen Idec Inc, Translat Neurol, Cambridge, MA USA
Tamas Revesz - UCL, Inst Neurol, Queen Sq Brain Bank Neurol Disorders, London, England
Olaf Riess - University of Tübingen
Fernando Rivadeneira - College Station Medical Center
Patrizia Rizzu - University of Amsterdam
Mina Ryten - UCL, Dept Mol Neurosci, Inst Neurol, London, England
Stephen Sawcer - University of Cambridge
Anthony Schapira - UCL, Inst Neurol, Dept Clin Neurosci, London, England
Hans Scheffer - Radboud University Nijmegen
Karen Shaw - UCL, Inst Neurol, Queen Sq Brain Bank Neurol Disorders, London, England
Ira Shoulson - University of Rochester
Ellen Sidransky - College Station Medical Center
Rohan de Silva - UCL, Dept Mol Neurosci, Inst Neurol, London, England
Colin Smith - University of Edinburgh
Chris C. A. Spencer - University of Oxford
Hreinn Stefansson - 14 DeCODE Genet, Reykjavik, Iceland
Stacy Steinberg - 14 DeCODE Genet, Reykjavik, Iceland
Joanna D. Stockton - University of Birmingham
Amy Strange - Wellcome Trust
Zhan Su - Wellcome Trust
Kevin Talbot - University of Oxford
Carlie M. Tanner - Parkinsons Inst & Clin Ctr, Dept Clin Res, Sunnyvale, CA USA
Avazeh Tashakkori-Ghanbaria - Wellcome Sanger Institute
Francois Tison - Hop Haut Leveque, Serv Neurol, Pessac, France
Daniah Trabzuni - UCL, Dept Mol Neurosci, Inst Neurol, London, England
Bryan J. Traynor - NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Andre G. Uitterlinden - College Station Medical Center
Jana Vandrovcova - UCL, Dept Mol Neurosci, Inst Neurol, London, England
Daan Velseboer - University of Amsterdam
Marie Vidailhet - Inserm
Damjan Vukcevic - Wellcome Trust
Robert Walker - University of Edinburgh
Bart van de Warrenburg - Radboud University Nijmegen
Michael E. Weale - College Station Medical Center
Mirdhu Wickremaratchi - Cardiff University
Nigel Williams - Cardiff University
Caroline H. Williams-Gray - University of Cambridge
Sophie Winder-Rhodes - University of Cambridge
Kari Stefansson - 14 DeCODE Genet, Reykjavik, Iceland
Maria Martinez - Inserm
Peter Donnelly - Wellcome Trust
Andrew B. Singleton - NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
John Hardy - UCL, Dept Mol Neurosci, Inst Neurol, London, England
Peter Heutink - University of Amsterdam
Alexis Brice - Inserm
Thomas Gasser - University of Tübingen
Nicholas W. Wood - UCL, UCL Genet Inst, London, England
WTCCC2
Publication Details: PLoS genetics, Vol.7(6), pp.e1002142-e1002142
Publisher: Public Library Science
Number of pages: 9
Grant note: 085475/B/08/Z; 085475/Z/08/Z / Wellcome Trust Icelandic Research Council J-0901; J-0804; G-0907 / Parkinson's UK NS057105; RR024992 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Reta Lila Weston Trust for Medical Research ART-PPG2011A-14 / Alzheimers Research UK; Alzheimer's Research UK (ARUK) HA-215 / Helmholtz Association 8047; J-0804 / Parkinson's UK G0901254 / UK Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Landspitali University Hospital Wolfson-Royal Society; Royal Society MC_G1000735; G0501560; G0901254; G0900627; G1100616; G0700943; G0400017; G1100479; MC_PC_09003; G0800784; G0801418B; G0701075; G0802462; G0800784B; MC_G0901330 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) State of Bavaria German Federal Ministry of Education, Science, Research, and Technology ANR-08-MNP-012 / French National Agency of Research; Agence Nationale de la Recherche (ANR) PIAP-GA-2008-230596 MarkMD / European Community; European Commission ForschungszentrumfurUmwelt und Gesundheit (GSF) 01GR0468 / German Federal Ministry of Education and Research (BMBF) NGFN; Federal Ministry of Education & Research (BMBF) 01GS08134 / German National Genome Network (NGFNplus) G0700943 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Z01 AG000949-02; Z01-ES101986 / National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services Department of Health NIHR Biomedical Research Centre; National Institutes of Health Research (NIHR) American Parkinson Disease Association (APDA) W81XWH-09-2-0128 / US Department of Defense; United States Department of Defense G1100616; G0700943; G0701075; G0501560; G0900627; G0901254; G1100479; MC_PC_09003; MC_G1000735; G0800784; G0802462; MC_G0901330; G0400017 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Barnes Jewish Hospital Foundation WT089698 / Wellcome Trust/MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); Wellcome Trust ANR-08-NEUR-004-01 / National Research Funding Agency
Identifiers: 9935017708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article