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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease

PLoS ONE · 2014 · Vol. 9(6) · pp. e94661–e94661

Valentina Escott‐Price(Cardiff University)Céline Bellenguez(Institut Pasteur de Lille)Li‐San Wang(University of Pennsylvania)Seung‐Hoan Choi(Boston University)Denise Harold(Cardiff University)Lesley Jones(Cardiff University)Peter Holmans(Cardiff University)Amy Gerrish(Cardiff University)Alexey Vedernikov(Cardiff University)Alexander Richards(Cardiff University)Anita L. DeStefano(Boston University)Jean‐Charles Lambert(Inserm)Carla A. Ibrahim‐Verbaas(Erasmus MC)Adam C. Naj(University of Pennsylvania)Rebecca Sims(Cardiff University)Gyungah Jun(Boston University)Joshua C. Bis(University of Washington)Gary W. Beecham(Dr. John T. Macdonald Foundation)Benjamin Grenier‐Boley(Université de Lille)Giancarlo Russo(University of Zurich)Tricia A. Thornton‐Wells(Vanderbilt University)Nicola Denning(Cardiff University)Albert V. Smith(University of Iceland)Vincent Chouraki(Boston University)Charlene Thomas(Cardiff University)M. Arfan Ikram(Netherlands Consortium for Healthy Ageing)Diana ZélénikaBadri N. Vardarajan(Boston University)Yoichiro Kamatani(Fondation Jean Dausset-CEPH)Chiao‐Feng Lin(University of Pennsylvania)Helena Schmidt(Medical University of Graz)Brian W. Kunkle(University of Miami)Melanie Dunstan(Cardiff University)Maria Vronskaya(Cardiff University)Andrew D. Johnson(Framingham Heart Study)Agustı́n Ruiz(Fundació ACE)Marie‐Thérèse BihoreauChristiane Reitz(Columbia University)Florence Pasquier(Centre Hospitalier Universitaire de Lille)Paul Hollingworth(Cardiff University)Olivier Hanon(Université Paris Cité)Annette L. Fitzpatrick(University of Washington)Joseph D. Buxbaum(Icahn School of Medicine at Mount Sinai)Dominique Campion(Université de Rouen Normandie)Paul K. Crane(University of Washington)Clinton T. Baldwin(Boston University)Tim Becker(German Center for Neurodegenerative Diseases)Vilmundur Guðnason(Icelandic Heart Association)Carlos Cruchaga(Hope Center for Neurological Disorders)David Craig(Queen's University Belfast)Najaf Amin(Erasmus MC)Claudine Berr(Inserm)Lorna M. Lopez(University of Pittsburgh)Philip L. De Jager(Harvard University)Vincent Deramecourt(Université de Lille)Janet Johnston(Queen's University Belfast)Denis A. Evans(Rush University Medical Center)Simon Lovestone(King's College London)Luc Letenneur(Inserm)Isabel Hernández(Fundació ACE)David C. Rubinsztein(University of Cambridge)Gudny Eiriksdottir(Icelandic Heart Association)Kristel Sleegers(University of Antwerp)Alison Goate(Hope Center for Neurological Disorders)Nathalie Fiévet(Institut Pasteur de Lille)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(Stockholm University)Pascale Barberger‐Gateau(King's College London)Bernadette McGuinness(Queen's University Belfast)Eric B. Larson(Kaiser Permanente Washington Health Research Institute)Amanda Myers(University of Miami)Carole Dufouil(Inserm)Stephen Todd(Queen's University Belfast)David Wallon(Inserm)Seth Love(Frenchay Hospital)Ekaterina Rogaeva(Occupational Cancer Research Centre)John Gallacher(Cardiff University)Peter St George‐Hyslop(University of Toronto)Jordi Clarimón(Biomedical Research Networking Center on Neurodegenerative Diseases)Alberto Lleó(Universitat Autònoma de Barcelona)Antony Bayer(Cardiff University)Debby W. Tsuang(University of Washington)Lei Yu(Rush University Medical Center)Magda Tsolaki(Aristotle University of Thessaloniki)Paola Bossù(Fondazione Santa Lucia)Gianfranco Spalletta(Fondazione Santa Lucia)Petroula Proitsi(King's College London)John Collinge(University College London)Sandro Sorbi(University of Florence)Florentino Sánchez-García(Hospital Universitario de Gran Canaria Doctor Negrín)Nick C. Fox(University College London)John HardyMaría Cándida Déniz Naranjo(Hospital Universitario de Gran Canaria Doctor Negrín)Paolo Bosco(Istituti di Ricovero e Cura a Carattere Scientifico)Robert Clarke(University of Oxford)Carol Brayne(University of Cambridge)Daniela Galimberti(Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico)Elio Scarpini(University of Milan)Ubaldo Bonuccelli(University of Pisa)Michelangelo Mancuso(University of Pisa)Gabriele Siciliano(University of Pisa)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(Ludwig-Maximilians-Universität München)Alberto Pilotto(Casa Sollievo della Sofferenza)Ana Frank(Biomedical Research Networking Center on Neurodegenerative Diseases)Francesco Panza(University of Bari Aldo Moro)Vincenzo Solfrizzi(University of Bari Aldo Moro)Paolo Caffarra(University of Parma)Benedetta Nacmias(University of Florence)William Perry(University of Miami)Manuel Mayhaus(Saarland University)Lars Lannfelt(Uppsala University)Håkon Håkonarson(Children's Hospital of Philadelphia)Sabrina Pichler(Saarland University)Minerva M. Carrasquillo(Mayo Clinic in Florida)Martin Ingelsson(Uppsala University)Duane Beekly(University of Washington)Victoria Álvarez(Universidad de Oviedo)Fanggeng Zou(Mayo Clinic in Florida)Otto Valladares(University of Pennsylvania)Steven G. Younkin(Mayo Clinic in Florida)Eliécer Coto(Universidad de Oviedo)Kara L. Hamilton‐Nelson(Dr. John T. Macdonald Foundation)Wei Gu(Saarland University)Cristina Razquín(Universidad de Navarra)Pau Pástor(Instituto de Salud Carlos III)Ignacio Mateo(Universidad de Cantabria)Michael J. Owen(Cardiff University)Kelley M. Faber(Indiana University – Purdue University Indianapolis)Pálmi V. Jónsson(National University Hospital of Iceland)Onofre Combarros(Universidad de Cantabria)Michael O’Donovan(Cardiff University)Laura B. Cantwell(University of Pennsylvania)Hilkka Soininen(University of Eastern Finland)Deborah Blacker(Massachusetts General Hospital)Simon Mead(MRC Prion Unit)Thomas H. Mosley(University of Mississippi Medical Center)David A. Bennett(Rush University Medical Center)Tamara B. HarrisLaura Fratiglioni(Stockholm University)Clive Holmes(University of Southampton)Renée F.A.G. de Bruijn(Erasmus MC)Peter Passmore(Queen's University Belfast)Thomas J. Montine(University of Washington)Karolien Bettens(University of Antwerp)Jerome I. Rotter(Harbor–UCLA Medical Center)Alexis Brice(Inserm)Kevin Morgan(Queen's Medical Centre)Tatiana Foroud(Indiana University – Purdue University Indianapolis)Walter A. Kukull(University of Washington)Didier Hannequin(Université de Rouen Normandie)John Powell(King's College London)Michael A. Nalls(National Institute on Aging)Karen Ritchie(Imperial College London)Kathryn L. Lunetta(Boston University)John S.K. Kauwe(Brigham Young University)Eric Boerwinkle(Baylor Genetics)Markus J. Riemenschneider(Saarland University)Merçé Boada(Universitat Autònoma de Barcelona)Mikko Hiltunen(Kuopio University Hospital)Eden R. Martin(Dr. John T. Macdonald Foundation)Reinhold Schmidt(Medical University of Graz)Dan Rujescu(Ludwig-Maximilians-Universität München)Jean‐François Dartigues(Inserm)Richard Mayeux(Columbia University)Christophe Tzourio(Inserm)Albert Hofman(Erasmus MC)Markus M. Nöthen(University of Bonn)Caroline Graff(Karolinska Institutet)Bruce M. Psaty(Kaiser Permanente Washington Health Research Institute)Jonathan L. Haines(Vanderbilt University)Mark Lathrop(Boston University)Margaret A. Pericak‐Vance(University of Miami)Lenore J. LaunerChristine Van Broeckhoven(VIB-UAntwerp Center for Molecular Neurology)Lindsay A. Farrer(Boston University)Cornelia M. van Duijn(Centre for Medical Systems Biology)Alfredo Ramı́rez(University of Bonn)Sudha Seshadri(Boston University)Gerard D. Schellenberg✉(University of Pennsylvania)Philippe Amouyel✉(Institut Pasteur de Lille)Julie Williams✉(Cardiff University)

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Abstract

The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

Alzheimer's disease research and treatments Bioinformatics and Genomic Networks Genetic Associations and EpidemiologyGeneticsBiologyGeneGenome-wide association studyDiseaseAlzheimer's diseaseDementiaGenomeGenetic associationGenotype

MeSH terms

Alzheimer DiseaseCarrier ProteinsHeat-Shock ProteinsHumansReceptors, Antigen, B-CellCase-Control StudiesPolymorphism, Single NucleotideGenome-Wide Association Study

Funding

Juvenile Diabetes Research Foundation International
Massachusetts General Hospital
University of Southern California
Vanderbilt University
University of Miami
University of Pennsylvania
Emory University
Northwestern University
School of Medicine, Boston University
University of Washington
Johns Hopkins University
University of Pittsburgh
Rush University
Wellcome Trust
Llywodraeth Cymru
Alzheimer's Society
Centro de Biología Molecular Severo Ochoa
Alzheimer's Research Trust
York University
Alzheimer Society
National Institute for Health and Care Research
Newcastle University
European Commission
Cardiff University
ZonMw
Bundesministerium für Bildung und Forschung
Austrian Science Fund
Erasmus Medisch Centrum
Ministero della Salute
Karolinska Institutet
Stockholms Läns Landsting
Vetenskapsrådet
North Bristol NHS Trust
Deutsches Zentrum für Neurodegenerative Erkrankungen
Swedish Brain Power
Hersenstichting
Internationale Stichting Alzheimer Onderzoek
University College London Hospitals NHS Foundation Trust
Karl-Franzens-Universität Graz
Medizinische Universität Graz
Marcus och Amalia Wallenbergs minnesfond
Hjartavernd
H. Lundbeck A/S
Heinz Nixdorf Stiftung
National Institutes of Health
University of California, Los Angeles
University of California, Davis
University of California, San Diego
University of California, San Francisco
University of California, Irvine
Medical Research Council
Menzies Centre for Australian Studies, King's College London, University of London
Instituto de Salud Carlos III
National Institute on Aging
National Heart, Lung, and Blood Institute
National Institute of Mental Health
National Human Genome Research Institute
National Eye Institute
National Institute on Deafness and Other Communication Disorders
National Institute of Allergy and Infectious Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
National Institute of Neurological Disorders and Stroke
National Institute of Child Health and Human Development
National Center for Advancing Translational Sciences