New Results
Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into the complex genetic architecture
Ruth Chia, Marya S. Sabir, Sara Bandres-Ciga, Sara Saez-Atienzar, Regina H. Reynolds, Emil Gustavsson, Ronald L. Walton, Sarah Ahmed, Coralie Viollet, Jinhui Ding, Mary B. Makarious, Monica Diez-Fairen, Makayla K. Portley, Zalak Shah, Yevgeniya Abramzon, Dena G. Hernandez, Cornelis Blauwendraat, David J. Stone, John Eicher, Laura Parkkinen, Olaf Ansorge, Lorraine Clark, Lawrence S. Honig, Karen Marder, Afina Lemstra, Peter St George-Hyslop, Elisabet Londos, Kevin Morgan, Tammaryn Lashley, Thomas T. Warner, Zane Jaunmuktane, Douglas Galasko, Isabel Santana, Pentti J. Tienari, Liisa Myllykangas, Minna Oinas, Nigel J. Cairns, John C. Morris, Glenda M. Halliday, Vivianna M. Van Deerlin, John Q. Trojanowski, Maurizio Grassano, Andrea Calvo, Gabriele Mora, Antonio Canosa, Gianluca Floris, Ryan C. Bohannan, Francesca Brett, Ziv Gan-Or, Joshua T. Geiger, Anni Moore, Patrick May, Rejko Krüger, David Goldstein, Grisel Lopez, Nahid Tayebi, Ellen Sidransky, the Fox Investigation for New Discovery of Biomarkers; The American Genome Center; Lucy Norcliffe-Kaufmann, Jose-Alberto Palma, Horacio Kaufmann, Vikram Shakkottai, Matthew Perkins, Kathy L. Newell, Thomas Gasser, Claudia Schulte, Francesco Landi, Erika Salvi, Daniele Cusi, Eliezer Masliah, Ronald C. Kim, Chad A. Caraway, Ed Monuki, Maura Brunetti, Ted M. Dawson, Liana S. Rosenthal, Marilyn S. Albert, Olga Pletnikova, Juan C. Troncoso, Margaret E. Flanagan, Qinwen Mao, Eileen H. Bigio, Eloy Rodríguez-Rodríguez, Jon Infante, Carmen Lage, Isabel González-Aramburu, Pascual Sanchez-Juan, Bernardino Ghetti, Julia Keith, Sandra E. Black, Mario Masellis, Ekaterina Rogaeva, Charles Duyckaerts, Alexis Brice, Suzanne Lesage, Georgia Xiromerisiou, Matthew J. Barrett, Bension S. Tilley, Steve Gentleman, Giancarlo Logroscino, Geidy E. Serrano, Thomas G. Beach, Ian G. McKeith, Alan J. Thomas, Johannes Attems, Christopher M. Morris, Laura Palmer, Seth Love, Claire Troakes, Safa Al-Sarraj, Angela K. Hodges, Dag Aarsland, Gregory Klein, Scott M. Kaiser, Randy Woltjer, Pau Pastor, Lynn M. Bekris, James Leverenz, Lilah M. Besser, Amanda Kuzma, Alan E. Renton, Alison Goate, David A. Bennett, Clemens R. Scherzer, Huw R. Morris, Raffaele Ferrari, Diego Albani, Stuart Pickering- Brown, Kelley Faber, Walter Kukull, Estrella Morenas-Rodriguez, Alberto Lleó, Juan Fortea, Daniel Alcolea, Jordi Clarimon, Michael A. Nalls, Luigi Ferrucci, Susan M. Resnick, Toshiko Tanaka, Tatiana M. Foroud, Neill R. Graff-Radford, Zbigniew K. Wszolek, Tanis Ferman, Bradley F. Boeve, John A. Hardy, Eric Topol, Ali Torkamani, Andrew B. Singleton, Mina Ryten, Dennis Dickson, Adriano Chiò, Owen A. Ross, J. Raphael Gibbs, Clifton L. Dalgard, Bryan J. Traynor, View ORCID ProfileSonja W. Scholz
doi: https://doi.org/10.1101/2020.07.06.185066
Ruth Chia
1Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
Marya S. Sabir
2Neurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Sara Bandres-Ciga
3Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
Sara Saez-Atienzar
1Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
Regina H. Reynolds
4Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK
5NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK
6Great Ormond Street Institute of Child Health, Genetics and Genomic Medicine, University College London, London, UK
Emil Gustavsson
5NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK
6Great Ormond Street Institute of Child Health, Genetics and Genomic Medicine, University College London, London, UK
Ronald L. Walton
7Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
Sarah Ahmed
2Neurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Coralie Viollet
8Department of Anatomy, Physiology and Genetics, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Jinhui Ding
9Computational Biology Core, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
Mary B. Makarious
2Neurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Monica Diez-Fairen
10Memory and Movement Disorders Units, Department of Neurology, University Hospital Mutua de Terrassa, Barcelona, Spain
Makayla K. Portley
2Neurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Zalak Shah
2Neurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Yevgeniya Abramzon
1Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
Dena G. Hernandez
3Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
Cornelis Blauwendraat
3Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
David J. Stone
11Cerevel Therapeutics, Boston, MA, USA
John Eicher
12Genetics and Pharmacogenomics, Merck & Co., Inc., West Point, PA, USA
Laura Parkkinen
13Nuffield Department of Clinical Neurosciences, Oxford Parkinson’s Disease Centre, University of Oxford, Oxford, UK
Olaf Ansorge
13Nuffield Department of Clinical Neurosciences, Oxford Parkinson’s Disease Centre, University of Oxford, Oxford, UK
Lorraine Clark
14Taub Institute for Alzheimer Disease and the Aging Brain and Department of Pathology and Cell Biology, Columbia University, New York, NY, USA
Lawrence S. Honig
14Taub Institute for Alzheimer Disease and the Aging Brain and Department of Pathology and Cell Biology, Columbia University, New York, NY, USA
Karen Marder
14Taub Institute for Alzheimer Disease and the Aging Brain and Department of Pathology and Cell Biology, Columbia University, New York, NY, USA
Afina Lemstra
15Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, Amsterdam, Netherlands
Peter St George-Hyslop
16Department of Neurosciences, Cambridge Institute of Medical Research, University of Cambridge, Cambridge, UK
17Department of Medicine, University of Toronto, Toronto, ON, Canada
Elisabet Londos
18Clinical Memory Research Unit, Institution of Clinical Sciences Malmo, Lund University, Lund, Sweden
Kevin Morgan
19Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK
Tammaryn Lashley
4Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK
20Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK
Thomas T. Warner
20Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK
21Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London, UK
Zane Jaunmuktane
20Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK
Douglas Galasko
22Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA
23Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA
Isabel Santana
24Neurology Service, University of Coimbra Hospital, Coimbra, Portugal
Pentti J. Tienari
25Translational Immunology, Research Programs Unit, University of Helsinki, Helsinki, Finland
26Department of Neurology, Helsinki University Hospital, Helsinki, Finland
Liisa Myllykangas
27Department of Pathology, Medicum, University of Helsinki, Helsinki, Finland
28HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland
Minna Oinas
29Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland
30Department of Clinical Medicine, Faculty of Health, UiT The Arctic University of Norway, Tromsø, Norway
Nigel J. Cairns
31Knight Alzheimer’s Disease Research Center, Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA
John C. Morris
31Knight Alzheimer’s Disease Research Center, Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA
Glenda M. Halliday
32Neuroscience Research Australia, Sydney, NSW, Australia
33School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
34Brain and Mind Centre, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
Vivianna M. Van Deerlin
35Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
John Q. Trojanowski
35Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Maurizio Grassano
36“Rita Levi Montalcini” Department of Neuroscience, University of Turin, Turin, Italy
1Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
Andrea Calvo
36“Rita Levi Montalcini” Department of Neuroscience, University of Turin, Turin, Italy
Gabriele Mora
37Istituti Clinici Scientifici Maugeri, IRCCS, Milan, Italy
Antonio Canosa
36“Rita Levi Montalcini” Department of Neuroscience, University of Turin, Turin, Italy
Gianluca Floris
38Department of Neurology, University Hospital of Cagliari, Cagliari, Italy
Ryan C. Bohannan
39Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA
Francesca Brett
40Dublin Brain Bank, Neuropathology Department, Beaumont Hospital, Dublin, Ireland
Ziv Gan-Or
41Montreal Neurological Institute and Hospital, Department of Neurology & Neurosurgery, McGill University, Montreal, QC, Canada
Joshua T. Geiger
2Neurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Anni Moore
9Computational Biology Core, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
Patrick May
42Luxembourg Center for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
Rejko Krüger
42Luxembourg Center for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
43Luxembourg Institute of Health (LIH), Strassen, Luxembourg
44Centre Hospitalier de Luxembourg (CHL), Luxembourg City, Luxembourg
David Goldstein
45Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Grisel Lopez
46Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA
Nahid Tayebi
46Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA
Ellen Sidransky
46Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA
47Department of Neurology, New York University School of Medicine, New York, NY, USA
Jose-Alberto Palma
47Department of Neurology, New York University School of Medicine, New York, NY, USA
Horacio Kaufmann
47Department of Neurology, New York University School of Medicine, New York, NY, USA
Vikram Shakkottai
48Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA
Matthew Perkins
49Michigan Brain Bank, University of Michigan Medical School, Ann Arbor, MI, USA
Kathy L. Newell
50Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
Thomas Gasser
51Department of Neurodegenerative Diseases and German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany
Claudia Schulte
51Department of Neurodegenerative Diseases and German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany
Francesco Landi
52Department of Gerontology and Geriatrics, Catholic University of the Sacred Heart, Rome, Italy
Erika Salvi
53Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
Daniele Cusi
54Bio4Dreams-Business Nursery for Life, Milan, Italy
Eliezer Masliah
55Molecular Neuropathology Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
Ronald C. Kim
56Department of Neuropathology, School of Medicine, University of California Irvine, Irvine, CA, USA
Chad A. Caraway
57Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA
Ed Monuki
58Department of Pathology & Laboratory Medicine, School of Medicine, University of California Irvine, Irvine, CA, USA
Maura Brunetti
36“Rita Levi Montalcini” Department of Neuroscience, University of Turin, Turin, Italy
Ted M. Dawson
59Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA
60Neuroregeneration and Stem Cell Programs, Institute of Cell Engineering, Johns Hopkins University Medical Center, Baltimore, MD, USA
61Department of Pharmacology and Molecular Science, Johns Hopkins University Medical Center, Baltimore, MD, USA
62Solomon H. Snyder Department of Neuroscience, Johns Hopkins University Medical Center, Baltimore, MD, USA
Liana S. Rosenthal
59Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA
Marilyn S. Albert
59Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA
Olga Pletnikova
63Department of Pathology (Neuropathology), Johns Hopkins University Medical Center, Baltimore, MD, USA
Juan C. Troncoso
63Department of Pathology (Neuropathology), Johns Hopkins University Medical Center, Baltimore, MD, USA
Margaret E. Flanagan
64Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Qinwen Mao
64Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Eileen H. Bigio
64Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Eloy Rodríguez-Rodríguez
65Neurology Service, University Hospital Marqués de Valdecilla-IDIVAL-UC-CIBERNED, Santander, Spain
Jon Infante
65Neurology Service, University Hospital Marqués de Valdecilla-IDIVAL-UC-CIBERNED, Santander, Spain
Carmen Lage
65Neurology Service, University Hospital Marqués de Valdecilla-IDIVAL-UC-CIBERNED, Santander, Spain
Isabel González-Aramburu
65Neurology Service, University Hospital Marqués de Valdecilla-IDIVAL-UC-CIBERNED, Santander, Spain
Pascual Sanchez-Juan
65Neurology Service, University Hospital Marqués de Valdecilla-IDIVAL-UC-CIBERNED, Santander, Spain
Bernardino Ghetti
50Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
Julia Keith
66Department of Anatomical Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
Sandra E. Black
67Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
68Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada
69Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
70Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
71LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
Mario Masellis
72Cognitive & Movement Disorders Clinic, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
73Department of Medicine, Division of Neurology, University of Toronto, Toronto, ON, Canada
70Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
71LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
Ekaterina Rogaeva
74Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada
Charles Duyckaerts
75Department of Neuropathology Escourolle, Paris Brain Institute, Sorbonne Universites, Paris, France
Alexis Brice
76Paris Brain Institute, Sorbonne Universites, Paris, France
Suzanne Lesage
76Paris Brain Institute, Sorbonne Universites, Paris, France
Georgia Xiromerisiou
77Department of Neurology, University Hospital of Larissa, University of Thessalia, Larissa, Greece
Matthew J. Barrett
78Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USA
Bension S. Tilley
79Neuropathology Unit, Department of Brain Sciences, Imperial College London, London, UK
Steve Gentleman
79Neuropathology Unit, Department of Brain Sciences, Imperial College London, London, UK
Giancarlo Logroscino
80Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, Bari, Italy
Geidy E. Serrano
81Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA
Thomas G. Beach
81Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA
Ian G. McKeith
82Mental Health, Newcastle Brain Tissue Resource, Translational and Clinical Research Institute, Biomedical Research Building, Newcastle University, Newcastle upon Tyne, UK
Alan J. Thomas
82Mental Health, Newcastle Brain Tissue Resource, Translational and Clinical Research Institute, Biomedical Research Building, Newcastle University, Newcastle upon Tyne, UK
Johannes Attems
82Mental Health, Newcastle Brain Tissue Resource, Translational and Clinical Research Institute, Biomedical Research Building, Newcastle University, Newcastle upon Tyne, UK
Christopher M. Morris
82Mental Health, Newcastle Brain Tissue Resource, Translational and Clinical Research Institute, Biomedical Research Building, Newcastle University, Newcastle upon Tyne, UK
Laura Palmer
83South West Dementia Brain Bank, Bristol Medical School, University of Bristol, Bristol, UK
Seth Love
84Dementia Research Group, School of Clinical Sciences, University of Bristol, Bristol, UK
Claire Troakes
85Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, UK
Safa Al-Sarraj
86Department of Clinical Neuropathology and London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College Hospital and King’s College London, London, UK
Angela K. Hodges
85Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, UK
Dag Aarsland
85Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, UK
Gregory Klein
87Rush Alzheimer’s Disease Center, Rush University, Chicago, IL, USA
Scott M. Kaiser
88Department of Neuropathology, Indiana University School of Medicine, Indianapolis, IN, USA
Randy Woltjer
89Department of Neurology, Oregon Health & Sciences University, Portland, OR, USA
Pau Pastor
10Memory and Movement Disorders Units, Department of Neurology, University Hospital Mutua de Terrassa, Barcelona, Spain
Lynn M. Bekris
90Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
James Leverenz
91Cleveland Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA
Lilah M. Besser
92Institute for Human Health and Disease Intervention, Florida Atlantic University, Boca Raton, FL, USA
Amanda Kuzma
93Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Alan E. Renton
94Ronald M. Loeb Center for Alzheimer’s Disease, Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Alison Goate
95Ronald M. Loeb Center for Alzheimer’s Disease, Nash Family Department of Neuroscience, Department of Genetics and Genomic Sciences, and Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
David A. Bennett
87Rush Alzheimer’s Disease Center, Rush University, Chicago, IL, USA
Clemens R. Scherzer
96Precision Neurology Program, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA
Huw R. Morris
97Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London, UK
Raffaele Ferrari
4Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK
Diego Albani
98Laboratory of Biology of Neurodegenerative Disorders, Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
Stuart Pickering- Brown
99Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
Kelley Faber
100Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
Walter Kukull
101National Alzheimer’s Coordinating Center (NACC), University of Washington, Seattle, WA, USA
Estrella Morenas-Rodriguez
102Biomedizinisches Centrum (BMC), Biochemie, Ludwig-Maximilians-Universität München & Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Munich, Germany
103Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
104The Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Alberto Lleó
103Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
104The Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Juan Fortea
103Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
104The Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Daniel Alcolea
103Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
104The Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Jordi Clarimon
103Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
104The Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Michael A. Nalls
105Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
106Data Tecnica International, Glen Echo, MD, USA
Luigi Ferrucci
107Longitudinal Studies Section, National Institute on Aging, Baltimore, MD, USA
Susan M. Resnick
108Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA
Toshiko Tanaka
107Longitudinal Studies Section, National Institute on Aging, Baltimore, MD, USA
Tatiana M. Foroud
100Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
Neill R. Graff-Radford
109Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
Zbigniew K. Wszolek
109Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
Tanis Ferman
110Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA
Bradley F. Boeve
111Department of Neurology, Mayo Clinic, Rochester, MN, USA
John A. Hardy
4Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK
112UK Dementia Research Institute of UCL, UCL Institute of Neurology, University College London, London, UK
21Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London, UK
113UCL Movement Disorders Centre, University College London, London, UK
114Institute for Advanced Study, The Hong Kong University of Science and Technology, Hong Kong SAR, China
Eric Topol
115Scripps Research Translational Institute, Scripps Research, La Jolla, CA, USA
Ali Torkamani
115Scripps Research Translational Institute, Scripps Research, La Jolla, CA, USA
Andrew B. Singleton
3Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
Mina Ryten
5NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK
6Great Ormond Street Institute of Child Health, Genetics and Genomic Medicine, University College London, London, UK
Dennis Dickson
7Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
Adriano Chiò
36“Rita Levi Montalcini” Department of Neuroscience, University of Turin, Turin, Italy
116Institute of Cognitive Sciences and Technologies, C.N.R., Rome, Italy
117Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy
Owen A. Ross
7Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
118Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, USA
J. Raphael Gibbs
9Computational Biology Core, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
Clifton L. Dalgard
8Department of Anatomy, Physiology and Genetics, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Bryan J. Traynor
1Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
59Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA
Sonja W. Scholz
2Neurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
59Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA
Abstract
The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer’s and Parkinson’s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.
Competing Interest Statement
Thomas G. Beach is a consultant for Prothena, Vivid Genomics and Avid Radiopharmaceuticals. He is a scientific advisory board member for Vivid Genomics. John A. Hardy, Huw R. Morris, Stuart Pickering-Brown, Andrew B. Singleton, and Bryan J. Traynor hold US, EU and Canadian patents on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion of C9orf72. Michael A. Nalls is supported by a consulting contract between Data Tecnica International and the National Institute on Aging, NIH, Bethesda, MD, USA; as a possible conflict of interest Dr. Nalls also consults for Neuron23 Inc., Lysosomal Therapeutics Inc., Illumina Inc., the Michael J. Fox Foundation and Vivid Genomics among others. Jose A. Palma is an editorial board member of Movement Disorders, Parkinsonism & Related Disorders, BMC Neurology, and Clinical Autonomic Research. Bradley F. Boeve, James Leverenz, and Sonja W. Scholz serve on the Scientific Advisory Council of the Lewy Body Dementia Association. Sonja W. Scholz is an editorial board member for the Journal of Parkinson's Disease. Bryan J. Traynor is an editorial board member for JAMA Neurology; Journal of Neurology, Neurosurgery, and Psychiatry; Brain; and Neurobiology of Aging. Zbigniew K. Wszolek serves as a principal investigator or co-principal investigator on Abbvie, Inc. (M15-562 and M15-563), Biogen, Inc. (228PD201) grant, and Biohaven Pharmaceuticals, Inc. (BHV4157-206 and BHV3241-301). Zbigniew K. Wszolek serves as the principal investigator of the Mayo Clinic American Parkinson Disease Association (APDA) Information and Referral Center, and as co-principal investigator of the Mayo Clinic APDA Center for Advanced Research. All other authors report no competing interests.
Footnotes
↵# These authors are joint last authors.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
Posted July 06, 2020.
Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into the complex genetic architecture
Ruth Chia, Marya S. Sabir, Sara Bandres-Ciga, Sara Saez-Atienzar, Regina H. Reynolds, Emil Gustavsson, Ronald L. Walton, Sarah Ahmed, Coralie Viollet, Jinhui Ding, Mary B. Makarious, Monica Diez-Fairen, Makayla K. Portley, Zalak Shah, Yevgeniya Abramzon, Dena G. Hernandez, Cornelis Blauwendraat, David J. Stone, John Eicher, Laura Parkkinen, Olaf Ansorge, Lorraine Clark, Lawrence S. Honig, Karen Marder, Afina Lemstra, Peter St George-Hyslop, Elisabet Londos, Kevin Morgan, Tammaryn Lashley, Thomas T. Warner, Zane Jaunmuktane, Douglas Galasko, Isabel Santana, Pentti J. Tienari, Liisa Myllykangas, Minna Oinas, Nigel J. Cairns, John C. Morris, Glenda M. Halliday, Vivianna M. Van Deerlin, John Q. Trojanowski, Maurizio Grassano, Andrea Calvo, Gabriele Mora, Antonio Canosa, Gianluca Floris, Ryan C. Bohannan, Francesca Brett, Ziv Gan-Or, Joshua T. Geiger, Anni Moore, Patrick May, Rejko Krüger, David Goldstein, Grisel Lopez, Nahid Tayebi, Ellen Sidransky, the Fox Investigation for New Discovery of Biomarkers; The American Genome Center; Lucy Norcliffe-Kaufmann, Jose-Alberto Palma, Horacio Kaufmann, Vikram Shakkottai, Matthew Perkins, Kathy L. Newell, Thomas Gasser, Claudia Schulte, Francesco Landi, Erika Salvi, Daniele Cusi, Eliezer Masliah, Ronald C. Kim, Chad A. Caraway, Ed Monuki, Maura Brunetti, Ted M. Dawson, Liana S. Rosenthal, Marilyn S. Albert, Olga Pletnikova, Juan C. Troncoso, Margaret E. Flanagan, Qinwen Mao, Eileen H. Bigio, Eloy Rodríguez-Rodríguez, Jon Infante, Carmen Lage, Isabel González-Aramburu, Pascual Sanchez-Juan, Bernardino Ghetti, Julia Keith, Sandra E. Black, Mario Masellis, Ekaterina Rogaeva, Charles Duyckaerts, Alexis Brice, Suzanne Lesage, Georgia Xiromerisiou, Matthew J. Barrett, Bension S. Tilley, Steve Gentleman, Giancarlo Logroscino, Geidy E. Serrano, Thomas G. Beach, Ian G. McKeith, Alan J. Thomas, Johannes Attems, Christopher M. Morris, Laura Palmer, Seth Love, Claire Troakes, Safa Al-Sarraj, Angela K. Hodges, Dag Aarsland, Gregory Klein, Scott M. Kaiser, Randy Woltjer, Pau Pastor, Lynn M. Bekris, James Leverenz, Lilah M. Besser, Amanda Kuzma, Alan E. Renton, Alison Goate, David A. Bennett, Clemens R. Scherzer, Huw R. Morris, Raffaele Ferrari, Diego Albani, Stuart Pickering- Brown, Kelley Faber, Walter Kukull, Estrella Morenas-Rodriguez, Alberto Lleó, Juan Fortea, Daniel Alcolea, Jordi Clarimon, Michael A. Nalls, Luigi Ferrucci, Susan M. Resnick, Toshiko Tanaka, Tatiana M. Foroud, Neill R. Graff-Radford, Zbigniew K. Wszolek, Tanis Ferman, Bradley F. Boeve, John A. Hardy, Eric Topol, Ali Torkamani, Andrew B. Singleton, Mina Ryten, Dennis Dickson, Adriano Chiò, Owen A. Ross, J. Raphael Gibbs, Clifton L. Dalgard, Bryan J. Traynor, Sonja W. Scholz
bioRxiv 2020.07.06.185066; doi: https://doi.org/10.1101/2020.07.06.185066
Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into the complex genetic architecture
Ruth Chia, Marya S. Sabir, Sara Bandres-Ciga, Sara Saez-Atienzar, Regina H. Reynolds, Emil Gustavsson, Ronald L. Walton, Sarah Ahmed, Coralie Viollet, Jinhui Ding, Mary B. Makarious, Monica Diez-Fairen, Makayla K. Portley, Zalak Shah, Yevgeniya Abramzon, Dena G. Hernandez, Cornelis Blauwendraat, David J. Stone, John Eicher, Laura Parkkinen, Olaf Ansorge, Lorraine Clark, Lawrence S. Honig, Karen Marder, Afina Lemstra, Peter St George-Hyslop, Elisabet Londos, Kevin Morgan, Tammaryn Lashley, Thomas T. Warner, Zane Jaunmuktane, Douglas Galasko, Isabel Santana, Pentti J. Tienari, Liisa Myllykangas, Minna Oinas, Nigel J. Cairns, John C. Morris, Glenda M. Halliday, Vivianna M. Van Deerlin, John Q. Trojanowski, Maurizio Grassano, Andrea Calvo, Gabriele Mora, Antonio Canosa, Gianluca Floris, Ryan C. Bohannan, Francesca Brett, Ziv Gan-Or, Joshua T. Geiger, Anni Moore, Patrick May, Rejko Krüger, David Goldstein, Grisel Lopez, Nahid Tayebi, Ellen Sidransky, the Fox Investigation for New Discovery of Biomarkers; The American Genome Center; Lucy Norcliffe-Kaufmann, Jose-Alberto Palma, Horacio Kaufmann, Vikram Shakkottai, Matthew Perkins, Kathy L. Newell, Thomas Gasser, Claudia Schulte, Francesco Landi, Erika Salvi, Daniele Cusi, Eliezer Masliah, Ronald C. Kim, Chad A. Caraway, Ed Monuki, Maura Brunetti, Ted M. Dawson, Liana S. Rosenthal, Marilyn S. Albert, Olga Pletnikova, Juan C. Troncoso, Margaret E. Flanagan, Qinwen Mao, Eileen H. Bigio, Eloy Rodríguez-Rodríguez, Jon Infante, Carmen Lage, Isabel González-Aramburu, Pascual Sanchez-Juan, Bernardino Ghetti, Julia Keith, Sandra E. Black, Mario Masellis, Ekaterina Rogaeva, Charles Duyckaerts, Alexis Brice, Suzanne Lesage, Georgia Xiromerisiou, Matthew J. Barrett, Bension S. Tilley, Steve Gentleman, Giancarlo Logroscino, Geidy E. Serrano, Thomas G. Beach, Ian G. McKeith, Alan J. Thomas, Johannes Attems, Christopher M. Morris, Laura Palmer, Seth Love, Claire Troakes, Safa Al-Sarraj, Angela K. Hodges, Dag Aarsland, Gregory Klein, Scott M. Kaiser, Randy Woltjer, Pau Pastor, Lynn M. Bekris, James Leverenz, Lilah M. Besser, Amanda Kuzma, Alan E. Renton, Alison Goate, David A. Bennett, Clemens R. Scherzer, Huw R. Morris, Raffaele Ferrari, Diego Albani, Stuart Pickering- Brown, Kelley Faber, Walter Kukull, Estrella Morenas-Rodriguez, Alberto Lleó, Juan Fortea, Daniel Alcolea, Jordi Clarimon, Michael A. Nalls, Luigi Ferrucci, Susan M. Resnick, Toshiko Tanaka, Tatiana M. Foroud, Neill R. Graff-Radford, Zbigniew K. Wszolek, Tanis Ferman, Bradley F. Boeve, John A. Hardy, Eric Topol, Ali Torkamani, Andrew B. Singleton, Mina Ryten, Dennis Dickson, Adriano Chiò, Owen A. Ross, J. Raphael Gibbs, Clifton L. Dalgard, Bryan J. Traynor, Sonja W. Scholz
bioRxiv 2020.07.06.185066; doi: https://doi.org/10.1101/2020.07.06.185066
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