Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
Risk for late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify f...
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| Vydáno v: | Nature genetics Ročník 51; číslo 3; s. 414 - 430 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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New York
Nature Publishing Group US
01.03.2019
Nature Publishing Group |
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| ISSN: | 1061-4036, 1546-1718, 1546-1718 |
| On-line přístup: | Získat plný text |
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| Abstract | Risk for late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (
IQCK
,
ACE
,
ADAM10
,
ADAMTS1
,
and
WWOX
), two of which (
ADAM10
,
ACE
) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer’s or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer’s disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (
P
= 1.32 × 10
−7
), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism. |
|---|---|
| AbstractList | Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10
), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education. Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education. Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aß processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 x 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education. Risk for late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer’s or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer’s disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10−7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education. Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and A beta processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 x 10(-7)), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education. Risk for late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci ( IQCK , ACE , ADAM10 , ADAMTS1 , and WWOX ), two of which ( ADAM10 , ACE ) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer’s or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer’s disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants ( P = 1.32 × 10 −7 ), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education. Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism. |
| Author | Schneider, Julie A. Ritchie, Karen Cuccaro, Michael L. Boada, Merce Peters, Oliver Fin, Bertrand Duara, Ranjan Frosch, Matthew P. Ciaramella, Antonio Fornage, Myriam Myers, Amanda J. Amin, Najaf Jakobsdottir, Johanna Heun, Reinhard Weintraub, Sandra Galimberti, Daniela Kilander, Lena Spina, Salvatore Ryan, Natalie S. Vonsattel, Jean Paul Eiriksdottir, Gudny Tarraga, Lluís Atwood, Craig S. Van Eldik, Linda J. Bennett, David Bonuccelli, Ubaldo de Rojas, Itziar Buxbaum, Joseph D. Wilcock, Gordon Rubinsztein, David C. Masullo, Carlo Vandenberghe, Rik Wiltfang, Jens Bayer, Anthony Dickson, Dennis W. Hamilton, Ronald L. Proitsi, Petra Paulson, Henry L. Diez-Fairen, Monica Gkatzima, Olymbia Vardy, Emma Beiser, Alexa S. Hakonarson, Hakon Moebus, Susanne Boerwinkle, Eric Baldwin, Clinton T. Lunetta, Kathryn L. Woltjer, Randall L. De Deyn, Peter P. Mateo, Ignacio Lin, Honghuang Hampel, Harald LaFerla, Frank M. Whitehead, Patrice Corcoran, Chris Honig, Lawrence S. Yu, Lei McCurry, Susan M. Schmidt, Reinhold Hiltunen, Mikko Lipton, Richard B. Riemenschneide |
| AuthorAffiliation | 215 Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA, USA 73 German Center for Neurodegenerative Diseases, Bonn, Germany 282 A list of members and affiliations appears in the Supplementary Note 199 Division of Genetics, Department of Medicine and Partners Center for Personalized Genetic Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA 304 Department of Ophthalmology, Boston University School of Medicine, Boston University, Boston, MA, USA 65 Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA 306 Department of Health Services, University of Washington, Seattle, WA, USA 44 Department of Neurodegenerative Disease, MRC Prion Unit at UCL, Institute of Prion Diseases, London, UK 169 Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA 305 Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA 27 Department of Ge |
| AuthorAffiliation_xml | – name: 262 Department of Epidemiology, Columbia University, New York, NY, USA – name: 233 Department of Medicine-Pulmonary, New York University, New York, NY, USA – name: 238 Institute of Primary Care and Public Health, Cardiff University, University Hospital of Wales, Cardiff, UK – name: 37 UK Dementia Research Institute at UCL, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK – name: 46 Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy – name: 242 Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany – name: 159 Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA – name: 54 Laboratory for Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium – name: 79 Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany – name: 100 Netherlands Consortium on Health Aging and National Genomics Initiative, Leiden, the Netherlands – name: 285 IdiPAZ, Instituto de Investigación Sanitaria la Paz, Madrid, Spain – name: 149 Institute of Memory and Alzheimer’s Disease, Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Paris, France – name: 66 Alzheimer’s Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA – name: 170 Department of Pathology and Immunology, Washington University, St. Louis, MO, USA – name: 83 Institute of Genetics, Queen’s Medical Centre, University of Nottingham, Nottingham, UK – name: 148 Brain & Spine Institute, Inserm U 1127, CNRS UMR 7225, Paris, France – name: 99 Department of Internal Medicine, Erasmus University Medical Center, Rotterdamt, the Netherlands – name: 277 Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA – name: 296 Memory Research and Resources Center, CMRR de Bordeaux, Bordeaux, France – name: 197 Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA – name: 111 Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA – name: 230 Joint Biobank Munich and KORA Biobank, Baltimore, MD, USA – name: 215 Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA, USA – name: 162 Swedish Medical Center, Seattle, WA, USA – name: 65 Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA – name: 56 Department of Psychiatry and Psychotherapy, University Hospital, Saarland, Germany – name: 140 Department of Neurology, Indiana University, Indianapolis, IN, USA – name: 174 Department of Molecular Neuroscience, UCL, Institute of Neurology, London, UK – name: 34 Faculty of Medicine, University of Iceland, Reykjavik, Iceland – name: 71 Theme Aging, Unit for Hereditary Dementias, Karolinska University Hospital-Solna, Stockholm, Sweden – name: 137 Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden – name: 245 Institute of Psychiatry, Psychology and Neuroscienceó, King’s College London, London, UK – name: 252 Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA – name: 39 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK – name: 227 Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Munich, Germany – name: 189 Department of Psychiatry, New York University, New York, NY, USA – name: 268 Department of Psychiatry, University of Southern California, Los Angeles, CA, USA – name: 51 Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany – name: 87 Department of Pathology, University of Washington, Seattle, WA, USA – name: 133 Departments of Neurology, Pharmacology & Neuroscience, Texas Tech University Health Science Center, Lubbock, TX, USA – name: 142 Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA – name: 179 Department of Neurology, Catholic University of Rome, Rome, Italy – name: 310 These authors contributed equally: Brian W. Kunkle, Benjamin Grenier-Boley, Jean Charles-Lambert, Margaret A. Pericak-Vance – name: 305 Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA – name: 187 Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA – name: 166 University of Kansas Alzheimer’s Disease Center, University of Kansas Medical Center, Kansas City, KS, USA – name: 175 Mental Health & Behavioral Science Service, Bruce W. Carter VA Medical Center, Miami, FL, USA – name: 202 Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA – name: 248 German Center for Neurodegenerative Diseases, Goettingen, Germany – name: 27 Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany – name: 88 Elderly and Psychiatric Disorders Department, Medical University of Lodz, Lodz, Poland – name: 167 Department of Experimental and Clinical Medicine, Neurological Institute, University of Pisa, Pisa, Italy – name: 249 IBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal – name: 261 Oxford Healthy Aging Project, Clinical Trial Service Unit, University of Oxford, Oxford, UK – name: 38 Neurology Service and CIBERNED, ‘Marqués de Valdecilla’ University Hospital (University of Cantabria and IDIVAL), Santander, Spain – name: 36 Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy – name: 112 University Paris Descartes, EA 4468, AP-HP, Geriatrics Department, Hôpital Broca, Paris, France – name: 210 Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Sevilla, Spain – name: 216 Department of Pathology, Boston University School of Medicine, Boston University, Boston, MA, USA – name: 53 Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA – name: 8 Department of Biostatistics and Epidemiology/Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA – name: 32 Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK – name: 304 Department of Ophthalmology, Boston University School of Medicine, Boston University, Boston, MA, USA – name: 69 Office of Strategy and Measurement, University of North Texas Health Science Center, Fort Worth, TX, USA – name: 91 Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA – name: 125 Department of Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK – name: 222 Institute for Stroke and Dementia Research, Klinikum der Universität München, Munich, Germany – name: 85 Section of Neuroscience, DIMEC-University of Parma, Parma, Italy – name: 183 Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA – name: 115 University of Bordeaux, Inserm 1219, Bordeaux, France – name: 4 Univ. Lille, U1167-Excellence Laboratory LabEx DISTALZ, Lille, France – name: 98 Memory Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain – name: 201 Department of Genetics, Washington University, St. Louis, MO, USA – name: 276 Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA – name: 84 Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA – name: 106 Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA – name: 144 Department of Medicine, University of Wisconsin, Madison, WI, USA – name: 237 School of Nursing Northwest Research Group on Aging, University of Washington, Seattle, WA, USA – name: 269 Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA – name: 61 Department of Psychiatry, Martin Luther University Halle-Wittenberg, Halle, Germany – name: 74 Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany – name: 109 Department of Psychiatry, University of Arizona, Phoenix, AZ, USA – name: 259 Division of Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA – name: 263 Oxford Project to Investigate Memory and Ageing, University of Oxford, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK – name: 67 Division of Clinical Neurosciences, School of Medicine, University of Southampton, Southampton, UK – name: 177 Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA – name: 161 Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia – name: 221 Department of Neurology, Emory University, Atlanta, GA, USA – name: 290 Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Autonomous University Barcelona, Barcelona, Spain – name: 143 Geriatric Research, Education and Clinical Center (GRECC), University of Wisconsin, Madison, WI, USA – name: 254 Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy – name: 146 AXA Research Fund & Sorbonne University Chair, Paris, France – name: 127 Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA – name: 234 Department of Neurology, University of Miami, Miami, FL, USA – name: 82 Alzheimer’s Disease Research Center, University of Pittsburgh, Pittsburgh, PA, USA – name: 86 FERB-Alzheimer Center, Gazzaniga (Bergamo), Italy – name: 97 Fundació per la Recerca Biomèdica i Social Mútua Terrassa, Terrassa, Barcelona, Spain – name: 129 Institut des Neurosciences Translationnelles de Paris, Institut du Cerveau et de la Moelle Épinière, Paris, France – name: 213 Department of Neurology, Oregon Health &Science University, Portland, OR, USA – name: 6 UK Dementia Research Institute at Cardiff, Cardiff University, Cardiff, UK |
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givenname: Lutz surname: Frölich fullname: Frölich, Lutz organization: Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg – sequence: 198 givenname: Peter surname: Passmore fullname: Passmore, Peter organization: Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast – sequence: 200 givenname: Jonathan M. orcidid: 0000-0003-2059-024X surname: Schott fullname: Schott, Jonathan M. organization: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology – sequence: 208 givenname: John F. surname: Powell fullname: Powell, John F. organization: Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London – sequence: 211 givenname: Jeffrey M. surname: Burns fullname: Burns, Jeffrey M. organization: University of Kansas Alzheimer’s Disease Center, University of Kansas Medical Center – sequence: 222 givenname: John surname: Hardy fullname: Hardy, John organization: Department of Molecular Neuroscience, UCL, Institute of Neurology – sequence: 225 givenname: Minerva M. surname: Carrasquillo fullname: Carrasquillo, Minerva M. organization: Department of Neuroscience, Mayo Clinic – sequence: 231 givenname: Elizabeth A. surname: Crocco fullname: Crocco, Elizabeth A. organization: Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami – sequence: 240 givenname: Kelley M. surname: Faber fullname: Faber, Kelley M. organization: Indiana Alzheimer’s Disease Center, Indiana University School of Medicine – sequence: 241 givenname: Martin surname: Scherer fullname: Scherer, Martin organization: Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf – sequence: 248 givenname: Steven surname: Ferris fullname: Ferris, Steven organization: Department of Psychiatry, New York University – sequence: 252 givenname: Douglas R. surname: Galasko fullname: Galasko, Douglas R. organization: Department of Neurosciences, University of California, San Diego – sequence: 256 givenname: Daniel H. surname: Geschwind fullname: Geschwind, Daniel H. organization: Neurogenetics Program, University of California, Los Angeles – sequence: 266 givenname: Lawrence S. surname: Honig fullname: Honig, Lawrence S. organization: Taub Institute on Alzheimer’s Disease and the Aging Brain, Department of Neurology, Columbia University – sequence: 267 givenname: Thomas D. surname: Cushion fullname: Cushion, Thomas D. organization: Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, UK Dementia Research Institute at Cardiff, Cardiff University – sequence: 269 givenname: Paul surname: Hollingworth fullname: Hollingworth, Paul organization: Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University – sequence: 270 givenname: Christine M. surname: Hulette fullname: Hulette, Christine M. organization: Department of Pathology, Duke University – sequence: 287 givenname: Frank surname: Jessen fullname: Jessen, Frank organization: German Center for Neurodegenerative Diseases, Department of Psychiatry and Psychotherapy, University of Bonn, Department of Psychiatry and Psychotherapy, University of Cologne – sequence: 294 givenname: James J. surname: Lah fullname: Lah, James J. organization: Department of Neurology, Emory University – sequence: 296 givenname: James B. surname: Leverenz fullname: Leverenz, James B. organization: Cleveland Clinic Lou Ruvo Center for Brain Health, Cleveland Clinic – sequence: 305 givenname: Kevin orcidid: 0000-0002-8217-2396 surname: Morgan fullname: Morgan, Kevin organization: Human Genetics, Schools of Life Sciences and Medicine, University of Nottingham – sequence: 310 givenname: Deborah C. surname: Mash fullname: Mash, Deborah C. organization: Department of Neurology, University of Miami – sequence: 316 givenname: Susan M. surname: McCurry fullname: McCurry, Susan M. organization: School of Nursing Northwest Research Group on Aging, University of Washington – sequence: 326 givenname: Carol A. surname: Miller fullname: Miller, Carol A. organization: Department of Pathology, University of Southern California – sequence: 330 givenname: Christopher E. surname: Shaw fullname: Shaw, Christopher E. organization: Institute of Psychiatry, Psychology and Neuroscienceó, King’s College London, UK Dementia Research Institute, King’s College London – sequence: 331 givenname: Amanda J. surname: Myers fullname: Myers, Amanda J. organization: Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami – sequence: 338 givenname: Henry L. surname: Paulson fullname: Paulson, Henry L. organization: Department of Neurology, University of Michigan, Michigan Alzheimer Disease Center – sequence: 342 givenname: Elaine surname: Peskind fullname: Peskind, Elaine organization: Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine – sequence: 343 givenname: David H. surname: Cribbs fullname: Cribbs, David H. organization: Department of Neurology, University of California, Irvine – sequence: 344 givenname: Martin surname: Rossor fullname: Rossor, Martin organization: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology – sequence: 345 givenname: Aimee surname: Pierce fullname: Pierce, Aimee organization: Department of Neurology, University of California, Irvine – sequence: 349 givenname: Huntington surname: Potter fullname: Potter, Huntington organization: Department of Neurology, University of Colorado School of Medicine – sequence: 350 givenname: Sandro surname: Sorbi fullname: Sorbi, Sandro organization: Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, IRCCS Fondazione Don Carlo Gnocchi – sequence: 361 givenname: Christiane surname: Reitz fullname: Reitz, Christiane organization: Taub Institute on Alzheimer’s Disease and the Aging Brain, Department of Neurology, Columbia University, Gertrude H. Sergievsky Center, Columbia University, Department of Epidemiology, Columbia University – sequence: 363 givenname: John M. surname: Ringman fullname: Ringman, John M. organization: Department of Neurology, Keck School of Medicine at the University of Southern California, Los Angeles – sequence: 369 givenname: Howard J. surname: Rosen fullname: Rosen, Howard J. organization: Department of Neurology, University of California, San Francisco – sequence: 374 givenname: Patrizia surname: Mecocci fullname: Mecocci, Patrizia organization: Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia – sequence: 381 givenname: Susan surname: Slifer fullname: Slifer, Susan organization: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine – sequence: 385 givenname: Salvatore surname: Spina fullname: Spina, Salvatore organization: Department of Pathology and Laboratory Medicine, Indiana University – sequence: 394 givenname: Harry V. surname: Vinters fullname: Vinters, Harry V. organization: Department of Neurology, University of California, Los Angeles, Department of Pathology and Laboratory Medicine, University of California, Los Angeles – sequence: 396 givenname: Sandra surname: Weintraub fullname: Weintraub, Sandra organization: Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University Feinberg School of Medicine, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine – sequence: 397 givenname: Kathleen A. surname: Welsh-Bohmer fullname: Welsh-Bohmer, Kathleen A. organization: Department of Neurology, Duke University, Department of Psychiatry and Behavioral Sciences, Duke University – sequence: 409 givenname: Paul K. surname: Crane fullname: Crane, Paul K. organization: Department of Medicine, University of Washington – sequence: 410 givenname: David surname: Bennett fullname: Bennett, David organization: Department of Neurological Sciences, Rush University Medical Center, Rush Alzheimer’s Disease Center, Rush University Medical Center – sequence: 413 givenname: Virginia surname: Boccardi fullname: Boccardi, Virginia organization: Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia – sequence: 417 givenname: Oscar L. surname: Lopez fullname: Lopez, Oscar L. organization: Department of Psychiatry, University of Pittsburgh, Alzheimer’s Disease Research Center, University of Pittsburgh, Department of Neurology, University of Pittsburgh – sequence: 419 givenname: Panagiotis orcidid: 0000-0001-9251-070X surname: Deloukas fullname: Deloukas, Panagiotis organization: The Wellcome Trust Sanger Institute – sequence: 420 givenname: Carlos orcidid: 0000-0002-0276-2899 surname: Cruchaga fullname: Cruchaga, Carlos organization: Department of Psychiatry, Washington University School of Medicine, Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine – sequence: 429 givenname: Claudine orcidid: 0000-0001-5254-7655 surname: Berr fullname: Berr, Claudine organization: Inserm U1061 Neuropsychiatry, La Colombière Hospital, Montpellier University – sequence: 433 givenname: Steven G. surname: Younkin fullname: Younkin, Steven G. organization: Department of Neuroscience, Mayo Clinic, Department of Neurology, Mayo Clinic – sequence: 443 givenname: Jordi surname: Clarimon fullname: Clarimon, Jordi organization: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Autonomous University Barcelona – sequence: 445 givenname: Reinhold surname: Schmidt fullname: Schmidt, Reinhold organization: Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz – sequence: 446 givenname: Lindsay A. surname: Farrer fullname: Farrer, Lindsay A. organization: Department of Neurology, Boston University School of Medicine, Department of Biostatistics, Boston University School of Public Health, Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Department of Ophthalmology, Boston University School of Medicine, Boston University, Department of Epidemiology, Boston University School of Public Health – sequence: 447 givenname: Christine orcidid: 0000-0003-0183-7665 surname: Van Broeckhoven fullname: Van Broeckhoven, Christine organization: Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Laboratory for Neurogenetics, Institute Born-Bunge, University of Antwerp – sequence: 448 givenname: Michael orcidid: 0000-0001-7073-2379 surname: C. O’Donovan fullname: C. O’Donovan, Michael organization: Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University – sequence: 451 givenname: Jonathan L. surname: Haines fullname: Haines, Jonathan L. organization: Institute for Computational Biology, Department of Population & Quantitative Health Sciences, Case Western Reserve University – sequence: 454 givenname: Vilmundur surname: Gudnason fullname: Gudnason, Vilmundur organization: Icelandic Heart Association, Faculty of Medicine, University of Iceland – sequence: 455 givenname: Richard surname: Mayeux fullname: Mayeux, Richard organization: Taub Institute on Alzheimer’s Disease and the Aging Brain, Department of Neurology, Columbia University, Gertrude H. Sergievsky Center, Columbia University, Department of Neurology, Columbia University – sequence: 463 givenname: Sudha surname: Seshadri fullname: Seshadri, Sudha organization: Framingham Heart Study, Department of Neurology, Boston University School of Medicine, Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases – sequence: 464 givenname: Julie surname: Williams fullname: Williams, Julie organization: Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, UK Dementia Research Institute at Cardiff, Cardiff University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30820047$$D View this record in MEDLINE/PubMed https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-167637$$DView record from Swedish Publication Index (Stockholms universitet) https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-379343$$DView record from Swedish Publication Index (Uppsala universitet) http://kipublications.ki.se/Default.aspx?queryparsed=id:140390500$$DView record from Swedish Publication Index (Karolinska Institutet) |
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| ContentType | Journal Article |
| Copyright | The Author(s), under exclusive licence to Springer Nature America, Inc. 2019 Copyright Nature Publishing Group Mar 2019 |
| Copyright_xml | – notice: The Author(s), under exclusive licence to Springer Nature America, Inc. 2019 – notice: Copyright Nature Publishing Group Mar 2019 |
| CorporateAuthor | Alzheimer Disease Genetics Consortium (ADGC) Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD/PERADES) Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE) The European Alzheimer’s Disease Initiative (EADI) European Alzheimer’s Disease Initiative (EADI) |
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| DOI | 10.1038/s41588-019-0358-2 |
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| Notes | ObjectType-Article-1 ObjectType-Evidence Based Healthcare-3 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ADGC. Study design or conception: A.C.N., A.A.-W., E.R.M., K.H.-N., A.B.K., B.N.V., G.W.B., O.V., M.Butkiewicz, W.B., Y.Song, G.D.S., M.A.P.-V. Sample contribution: S.Mukherjee, P.K.C., R.B., P.M.A., M.S.A., D. Beekly, D. Blacker, R.S. Doody, T.J.F., M.P.F., B.Ghetti, R.M.H., M.I.K., M.J.K., C.K., W.K., E.B.L., R.B.L., T.J.M., R.C.P., E.M.R., J.S.R., D.R.R., M. Sano, P.S.G.-H., D.W.T., C.K.W., R.L.A., L.G.A., S.E.A., S.A., C.S.A., C.T.B., L.L.B., S. Barral, T.G.B., J.T.B., E.H.B., T.D.B., B.F.B., J.D.B., A.Boxer, J.R.B., J.M.B., J.D.Buxbaum, N.J.C., C. Cao, C.S.C., C.M.C., R.M.C., H.C.C., D.H.C., E.A.C., C.DeCarli, M.Dick, R.D., N.R.G.-R., D.A.E., K.M.F., K.B.F., D.W.F., M.R.F., S.F., T.M.F., D.R.G., M.Gearing, D.H.G., J.R.G., R.C.G., J.H.G., R.L.H., L.E.H., L.S.H., M.J.H., C.M.H., B.T.H., G.P.J., E.A., L.W.J., G.R.J., A. Karydas, J.A.K., R.K., N.W.K., J.H.K., F.M.L., J.J.L., J.B.L., A.I.L., A.P.L., K.L.L., C.G.L., D.C.M., F.M., D.C.Mash, E.M., W.C.M., S.M.M., A.N.M., A.C.M., M.M., B.L.M., C.A.M., J.W.M., J.C.M., A.J.M., S.O., J.M.O., J.E.P., H.L.P., E.P., A.P., W.W.P., H.P., J.F.Q., A.Raj, M.R., B.R., C.R., J.M.R., E.D.R., E.R., H.J.R., R.N.R., M.A.S., A.J.S., M.L.C., J. Vance, J.A.S., L.S.S., W.W.S., A.G.S., J.A.Sonnen, S. Spina, R.A.S., R.H.S., R.E.T., J.Q.T., J.C.T., V.M.V.D., L.J.V.E., H.V.V., J.P.V., S.W., K.A.W.-B., K.C.W., J.Williamson, T.S.W., R.L.W., C.B.W., C.-E.Y., L.Y., D.B., P.L.D.J., C.Cruchaga, A.M.G., N.E.-T., S.G.Y., D.W.D., H.H., L.A.F., J.Haines, R.Mayeux, L.-S.W., G.D.S., M.A.P.-V. Data generation: B.W.K., K.H.-N., A.B.K., O.V., L.Q., Y.Z., W.P., S.Slifer, J.Malamon, B.A.D., P.W., L.B.C., M.A., M.Tang, J.R.G., L.-S.W. Analysis: B.W.K., A.C.N., A.A.-W., E.R.M., K.H.-N., A.B.K., M.Tang, M.M.C., B.N.V., G.W.B., O.V., M.Butkiewicz, W.B., Y.S., G.D.S., M.A.P.-V. Manuscript preparation: B.W.K., G.D.S., M.A.P.-V. Study supervision/ management: B.W.K., L.A.F., J.Haines, R.Mayeux, L.-S.W., G.D.S., M.A.P.-V. EADI. Study design or conception: P.A., J.-C.L. Sample contribution: K.S., M.Hiltunen, J.E., M.D.Z., I.M., F.S.-G., M.C.D.N., D.Wallon, S.E., R.V., P.D.D., A.Squassina, E.R.-R., C.M.-F., Y.A.B., H.T., V.Giedraitis, L.Kilander, R.Brundin, L.C., S.Helisalmi, A.M.K., A.Haapasalo, V.S., V.Frisardi, V.Deramecourt, N.F., O.H., C.Dufouil, A.Brice, K.R., B.D., H.Soininen, L.Fratiglioni, L.K., F.Panza, D.H., P.C., F.S., P.B., L.Lannfelt, F.P., M.Ingelsson, C.G., P.S.-J., A.L., J.Clarimon, C.Berr, S.D., J.-F.D., A.Pilotto, M.J.B., P.Bosco, E.C., G.N., D.C., C.V.B., P.A., J.-C.L. Data generation: R.O., J.-G.G., M.-L.M., D.Bacq, F.G., B.F., S.Meslage Analysis: B.G.-B., V.D., C.Bellenguez Manuscript preparation: B.G.-B., P.A., J.-C.L. Study supervision/management: J.-F.Deleuze, A.Boland, P.A., J.-C.L. GERAD/ PERADES. Study design or conception: R.Sims, M.C.O., M.J.O., A.R., P.A.H., J.W. Sample contribution: R.Raybould, T.Morgan, P.Hoffmann, D.Harold, O.P., N.D., N.C.F., J.T.H., Y.P., M.Daniilidou, J.U., D.Galimberti, E.Scarpini, J.Kornhuber, S.Sordon., M.Mayhaus, W.G., A.M.H., S.Lovestone, R.Sussams, C.Holmes, W.M., A.Kawalia, S.Moebus, J.Turton, J.Lord, I.K., A.L., B.L., M.Gill, M.D.-F., I.A., A.Ciaramella, C.Cupidi, R.G.M., R.Cecchetti, M.T., D.Craig, D.A., A.G., M.K., O.G., H.Hampel, D.C.R., L.F., B.M., J.A.J., P.Passmore, J.M.S., J.D.W., M.K.L., P.Proitsi, J.Powell, J.S.K.K., M.Mancuso, U.B., A.M., G.Livingston, N.J.B., J.Hardy, J.B., R.Guerreiro, E.F., C.Masullo, G.B., L.M., A.H., M.Scherer, M.Riemenschneider, R.Heun, H.K., M.Leber, I.H., I.G., M.Hull, J.M., K.Mayo, T.F., D.Drichel, T.D.C., P.Hollingworth, R.Marshall, A.Meggy, G.M., G.L., D.G., G.R., F.J., B.V., E.V., K.-H.J., M.Dichgans, D.Mann, S.P.-B., N.K., H.W., K.M., K.Brown, C.Medway, M.M.N., N.M.H., A.Daniele, A.Bayer, J.G., H.V.D.B., C.Brayne, S.R.-H., A.A.-C., C.E.S., J.Wiltfang, V.A., A.B.S., J.C., S.M., M.Rossor, N.S.R., B.N., S.Sorbi, E.S., G.S., C.Caltagirone, M.D.O., R.C., A.D.S., D.W., G.W., A.C.B., M.G., Y.B.-S., P.M., P.P., V.B., N.W., P.D., R.G., P.G.K., S.L., C.C., J.T., R.Munger, A.R., J.W. Data generation: R.Sims, R.Raybould, T.Morgan, P.Hoffmann, D.Harold, A.Gerrish, N.D., P.Hollingworth, R.Marshall, A.Meggy, A.R., J.W. Analysis: R.Sims, M.V., A.F., N.Badarinarayan, D.Harold, G.M., G.L., D.G., V.E.-P., A.R., J.W., P.A.H. Manuscript preparation: R.Sims, T.D.C., P.A.H., J.W. Study supervision/management: R.Sims, L.J., V.E.-P., A.R., P.A.H., J.W. CHARGE. Study design or conception: A.L.D., C.M.V.D., S.S. Sample contribution: J.C.B., A.Ruiz, I.D.R., L.M.R., I.Q., A.C., A.L.F., G.E., J.J.H., A.O., M.E.G., H.L., H.Comic, G.Roschupkin, S.Li, I.Hernández, Q.Y., A.S.B., L.T., T.H.M., WT.L., F.R., E.Boerwinkle, J.I.R., A.G.U., S.M.-G., O.L.L., M.B., M.F., N.A., L.J.L., M.A.I., H.S., R.S., V.G., B.M.P. Data generation: J.C.B., J.Jakobsdottir, A.Ruiz, A.V.S., X.J., S.-H.C., H.H.A., J.A.B., T.A., E.H., C.Sarnowski, D.V., L.A.C. Analysis: J.C.B., S.J.v.d.L., V.C., J.Jakobsdottir, Y.C., Y.Saba, S.Ahmad, A.Ruiz, A.V.S., C.C.W., C.M.V.D., S.S. Manuscript preparation: S.J.v.d.L., A.Ruiz, B.M.P., C.M.V.D., S.S. Study supervision/management: C.M.V.D., S.S. Author contributions |
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| Snippet | Risk for late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large... Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large... Risk for late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large... |
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| Title | Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing |
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