Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

Jean-Charles Lambert; Carla A. Ibrahim-Verbaas; Denise Harold; Adam C. Naj; Rebecca Sims; Celine Bellenguez; Gyungah Jun; Anita L. DeStefano; Joshua C. Bis; Gary W. Beecham; Benjamin Grenier-Boley; Giancarlo Russo; Tricia A. Thornton-Wells; Nicola Jones; Albert V. Smith; Vincent Chouraki; Charlene Thomas; M. Arfan Ikram; Diana Zelenika; Badri N. Vardarajan; Yoichiro Kamatani; Chiao-Feng Lin; Amy Gerrish; Helena Schmidt; Brian Kunkle; Melanie L. Dunstan; Agustin Ruiz; Marie-Therese Bihoreau; Seung-Hoan Choi; Christiane Reitz; Florence Pasquier; Paul Hollingworth; Alfredo Ramirez; Olivier Hanon; Annette L. Fitzpatrick; Joseph D. Buxbaum; Dominique Campion; Paul K. Crane; Clinton Baldwin; Tim Becker; Vilmundur Gudnason; Carlos Cruchaga; David Craig; Najaf Amin; Claudine Berr; Oscar L. Lopez; Philip L. De Jager; Vincent Deramecourt; Janet A. Johnston; Denis Evans; Simon Lovestone; Luc Letenneur; Francisco J. Moron; David C. Rubinsztein; Gudny Eiriksdottir; Kristel Sleegers; Alison M. Goate; Nathalie Fievet; Matthew J. Huentelman; Michael Gill; Kristelle Brown; M. Ilyas Kamboh; Lina Keller; Pascale Barberger-Gateau; Bernadette McGuinness; Eric B. Larson; Robert Green; Amanda J. Myers; Carole Dufouil; Stephen Todd; David Wallon; Seth Love; Ekaterina Rogaeva; John Gallacher; Peter St George-Hyslop; Jordi Clarimon; Alberto Lleo; Anthony Bayer; Debby W. Tsuang; Lei Yu; Magda Tsolaki; Paola Bossu; Gianfranco Spalletta; Petroula Proitsi; John Collinge; Sandro Sorbi; Florentino Sanchez-Garcia; Nick C. Fox; John Hardy; Maria Candida Deniz Naranjo; Paolo Bosco; Robert Clarke; Carol Brayne; Daniela Galimberti; Michelangelo Mancuso; Fiona Matthews; Susanne Moebus; Patrizia Mecocci; Maria Del Zompo; Wolfgang Maier; Harald Hampel; Alberto Pilotto; Maria Bullido; Francesco Panza; Paolo Caffarra; Benedetta Nacmias; John R. Gilbert; Manuel Mayhaus; Lars Lannfelt; Hakon Hakonarson; Sabrina Pichler; Minerva M. Carrasquillo; Martin Ingelsson; Duane Beekly; Victoria Alvarez; Fanggeng Zou; Otto Valladares; Steven G. Younkin; Eliecer Coto; Kara L. Hamilton-Nelson; Wei Gu; Cristina Razquin; Pau Pastor; Ignacio Mateo; Michael J. Owen; Kelley M. Faber; Palmi V. Jonsson; Onofre Combarros; Michael C. O'Donovan; Laura B. Cantwell; Hilkka Soininen; Deborah Blacker; Simon Mead; Thomas H. Mosley; David A. Bennett; Tamara B. Harris; Laura Fratiglioni; Clive Holmes; Renee F. A. G. de Bruijn; Peter Passmore; Thomas J. Montine; Karolien Bettens; Jerome I. Rotter; Alexis Brice; Kevin Morgan; Tatiana M. Foroud; Walter A. Kukull; Didier Hannequin; John F. Powell; Michael A. Nalls; Karen Ritchie; Kathryn L. Lunetta; John S. K. Kauwe; Eric Boerwinkle; Matthias Riemenschneider; Merce Boada; Mikko Hiltunen; Eden R. Martin; Reinhold Schmidt; Dan Rujescu; Li-San Wang; Jean-Francois Dartigues; Richard Mayeux; Christophe Tzourio; Albert Hofman; Markus M. Noethen; Caroline Graff; Bruce M. Psaty; Lesley Jones; Jonathan L. Haines; Peter A. Holmans; Mark Lathrop; Margaret A. Pericak-Vance; Lenore J. Launer; Lindsay A. Farrer; Cornelia M. van Duijn; Christine Van Broeckhoven; Valentina Moskvina; Sudha Seshadri; Julie Williams; Gerard D. Schellenberg; Philippe Amouyel; EADI; Panos Deloukas

doi:10.1038/ng.2802

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Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

Journal article

Peer reviewed

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

Jean-Charles Lambert, Carla A. Ibrahim-Verbaas, Denise Harold, Adam C. Naj, Rebecca Sims, Celine Bellenguez, Gyungah Jun, Anita L. DeStefano, Joshua C. Bis, Gary W. Beecham, …

Nature genetics, Vol.45(12), pp.1452-U206

01/12/2013

DOI: https://doi.org/10.1038/ng.2802

PMCID: PMC3896259

PMID: 24162737

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 x 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

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Title: Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
Creators - without role: Jean-Charles Lambert - Inserm
Carla A. Ibrahim-Verbaas - Erasmus MC
Denise Harold - Cardiff University
Adam C. Naj - University of Pennsylvania
Rebecca Sims - Cardiff University
Celine Bellenguez - Inserm
Gyungah Jun - Boston University
Anita L. DeStefano - Boston University
Joshua C. Bis - University of Washington
Gary W. Beecham - Dr. John T. Macdonald Foundation
Benjamin Grenier-Boley - Inserm
Giancarlo Russo - University of Zurich
Tricia A. Thornton-Wells - Vanderbilt University
Nicola Jones - Cardiff University
Albert V. Smith - University of Iceland
Vincent Chouraki - Inserm
Charlene Thomas - Cardiff University
M. Arfan Ikram - Erasmus MC
Diana Zelenika - Evry
Badri N. Vardarajan - Boston University
Yoichiro Kamatani - Fondation Jean Dausset-CEPH
Chiao-Feng Lin - University of Pennsylvania
Amy Gerrish - Cardiff University
Helena Schmidt - Medical University of Graz
Brian Kunkle - Dr. John T. Macdonald Foundation
Melanie L. Dunstan - Cardiff University
Agustin Ruiz - Fundació ACE
Marie-Therese Bihoreau - Evry
Seung-Hoan Choi - Boston University
Christiane Reitz - Columbia University
Florence Pasquier - University of Lille
Paul Hollingworth - Cardiff University
Alfredo Ramirez - University of Bonn
Olivier Hanon - Université Paris Cité
Annette L. Fitzpatrick - University of Washington
Joseph D. Buxbaum - Icahn School of Medicine at Mount Sinai
Dominique Campion - Inserm
Paul K. Crane - University of Washington
Clinton Baldwin - Boston University
Tim Becker - German Center for Neurodegenerative Diseases
Vilmundur Gudnason - University of Iceland
Carlos Cruchaga - Washington University in St. Louis
David Craig - Queen's University Belfast
Najaf Amin - Erasmus MC
Claudine Berr - Inserm
Oscar L. Lopez - University of Pittsburgh
Philip L. De Jager - Brigham and Women's Hospital
Vincent Deramecourt - University of Lille
Janet A. Johnston - Queen's University Belfast
Denis Evans - Rush University Medical Center
Simon Lovestone - King's College London
Luc Letenneur - Inserm
Francisco J. Moron - Neocodex, Dept Genom Estruct, Seville, Spain
David C. Rubinsztein - University of Cambridge
Gudny Eiriksdottir - Icelandic Heart Association
Kristel Sleegers - University of Antwerp
Alison M. Goate - Washington University in St. Louis
Nathalie Fievet - Inserm
Matthew J. Huentelman - Translational Genomics Research Institute
Michael Gill - Trinity College Dublin
Kristelle Brown - University of Nottingham
M. Ilyas Kamboh - University of Pittsburgh
Lina Keller - Karolinska Institutet
Pascale Barberger-Gateau - Inserm
Bernadette McGuinness - Queen's University Belfast
Eric B. Larson - University of Washington
Robert Green - Brigham and Women's Hospital
Amanda J. Myers - University of Miami
Carole Dufouil - Inserm
Stephen Todd - Queen's University Belfast
David Wallon - Université de Rouen Normandie
Seth Love - Frenchay Hospital
Ekaterina Rogaeva - Occupational Cancer Research Centre
John Gallacher - Cardiff University
Peter St George-Hyslop - University of Cambridge
Jordi Clarimon - Hospital de Sant Pau
Alberto Lleo - Hospital de Sant Pau
Anthony Bayer - University Hospital of Wales
Debby W. Tsuang - VA Puget Sound Health Care System
Lei Yu - Rush University Medical Center
Magda Tsolaki - Aristotle University of Thessaloniki
Paola Bossu - Fondazione Santa Lucia
Gianfranco Spalletta - Fondazione Santa Lucia
Petroula Proitsi - King's College London
John Collinge - MRC Prion Unit
Sandro Sorbi - University of Florence
Florentino Sanchez-Garcia - Hospital Universitario de Gran Canaria Doctor Negrín
Nick C. Fox - UK Dementia Research Institute
John Hardy - Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
Maria Candida Deniz Naranjo - Hospital Universitario de Gran Canaria Doctor Negrín
Paolo Bosco - Oasi Maria SS
Robert Clarke - University of Oxford
Carol Brayne - University of Cambridge
Daniela Galimberti - University of Milan
Michelangelo Mancuso - University of Pisa
Fiona Matthews - MRC Biostatistics Unit
Susanne Moebus - Institut für Medizinische Informatik, Biometrie und Epidemiologie
Patrizia Mecocci - University of Perugia
Maria Del Zompo - University of Cagliari
Wolfgang Maier - University of Bonn
Harald Hampel - Goethe University Frankfurt
Alberto Pilotto - CASA
Maria Bullido - Univ Autonoma Madrid, Consejo Super Invest Cient, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Francesco Panza - University of Bari Aldo Moro
Paolo Caffarra - University of Parma
Benedetta Nacmias - University of Florence
John R. Gilbert - University of Miami
Manuel Mayhaus - Saarland University
Lars Lannfelt - Uppsala University
Hakon Hakonarson - Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA
Sabrina Pichler - Saarland University
Minerva M. Carrasquillo - Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA
Martin Ingelsson - Uppsala University
Duane Beekly - University of Washington
Victoria Alvarez - Hosp Univ Cent Asturias, Oviedo, Spain
Fanggeng Zou - Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA
Otto Valladares - Supreme Council Of Health
Steven G. Younkin - Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA
Eliecer Coto - Hosp Univ Cent Asturias, Oviedo, Spain
Kara L. Hamilton-Nelson - University of Miami
Wei Gu - Saarland University
Cristina Razquin - Universidad de Navarra
Pau Pastor - Universidad de Navarra
Ignacio Mateo - Universidad de Cantabria
Michael J. Owen - Cardiff University
Kelley M. Faber - Indiana University
Palmi V. Jonsson - University of Iceland
Onofre Combarros - Universidad de Cantabria
Michael C. O'Donovan - Cardiff University
Laura B. Cantwell - Supreme Council Of Health
Hilkka Soininen - University of Eastern Finland
Deborah Blacker - Harvard University
Simon Mead - Massachusetts Rehabilitation Commission
Thomas H. Mosley - University of Mississippi
David A. Bennett - Rush University
Tamara B. Harris - University of Washington
Laura Fratiglioni - Karolinska Institutet
Clive Holmes - University of Southampton
Renee F. A. G. de Bruijn - Erasmus MC
Peter Passmore - Queens University
Thomas J. Montine - University of Washington
Karolien Bettens - University of Antwerp
Jerome I. Rotter - College Station Medical Center
Alexis Brice - Université Paris Cité
Kevin Morgan - University of Nottingham
Tatiana M. Foroud - Indiana University
Walter A. Kukull - University of Washington
Didier Hannequin - Inserm
John F. Powell - University of London
Michael A. Nalls - NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA
Karen Ritchie - Inserm
Kathryn L. Lunetta - Boston University
John S. K. Kauwe - Brigham Young University
Eric Boerwinkle - College Station Medical Center
Matthias Riemenschneider - Saarland University
Merce Boada - Memory Clin Fundacio Alzheimer Ctr Educ ACF, Inst Catala Neurociencies Aplicades, Barcelona, Spain
Mikko Hiltunen - University of Eastern Finland
Eden R. Martin - University of Miami
Reinhold Schmidt - University of Graz
Dan Rujescu - Univ Halle, Dept Psychiat, Halle, Germany
Li-San Wang - Supreme Council Of Health
Jean-Francois Dartigues - Inserm
Richard Mayeux - Columbia University
Christophe Tzourio - Inserm
Albert Hofman - Erasmus MC
Markus M. Noethen - University of Bonn
Caroline Graff - Rush University
Bruce M. Psaty - University of Washington
Lesley Jones - Cardiff University
Jonathan L. Haines - Vanderbilt University
Peter A. Holmans - Cardiff University
Mark Lathrop - Evry
Margaret A. Pericak-Vance - University of Miami
Lenore J. Launer - NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA
Lindsay A. Farrer - Boston University
Cornelia M. van Duijn - Erasmus MC
Christine Van Broeckhoven - University of Antwerp
Valentina Moskvina - Cardiff University
Sudha Seshadri - Boston University
Julie Williams - Cardiff University
Gerard D. Schellenberg - Supreme Council Of Health
Philippe Amouyel - Inserm
EADI
Panos Deloukas - King Abdulaziz University
Publication Details: Nature genetics, Vol.45(12), pp.1452-U206
Publisher: Springer Nature
Number of pages: 9
Grant note: U01 AG032984; R01 AG033193 / US National Institutes of Health, National Institute on Aging (NIH-NIA) FRC (Fondation pour la Recherche sur le Cerveau) Wellcome Trust NF-SI-0508-10123; NF-SI-0611-10084 / National Institute for Health Research; National Institute for Health Research (NIHR) Erasmus University INSERM; Institut National de la Sante et de la Recherche Medicale (Inserm) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer's Disease) US National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA MC_PC_14095; G0902227; MR/K013041/1; MC_U123160651; MC_U137686857; MC_G1000734; G0601846; MC_U123160657; G0801306; MC_U105292687 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Alzheimer's Association (Chicago, Illinois); Alzheimer's Association MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) French National Foundation on Alzheimer's Disease and Related Disorders Alzheimer's Research UK (ARUK) LABEX (Laboratory of Excellence Program Investment for the Future) Welsh government Rotary MC_U123160657; G0601846; MR/K013041/1; MC_U105292687; MC_U137686857; MC_PC_14095; MC_U123160651; MC_G1000734; G0801306; G0902227 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 164 / Alzheimer's Society Institut Pasteur de Lille Erasmus Medical Center ART-PhD2011-10; ART-BIG2009-1; ARUK-NCG2012B-1; ARUK-PG2014-1; ART-RF2007-3 / Alzheimers Research UK; Alzheimer's Research UK (ARUK)
Identifiers: 9937362008331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article