PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study.

Abstract Dementia with Lewy bodies is the second most common form of dementia in elderly people but has been overshadowed in the research field, partly because of similarities between dementia with Lewy bodies, Parkinson's disease, and Alzheimer's disease. So far, to our knowledge, no large-scale genetic study of dementia with Lewy bodies has been done. To better understand the genetic basis of dementia with Lewy bodies, we have done a genome-wide association study with the aim of identifying genetic risk factors for this disorder.
PMID
Related Publications
Authors

Mayor MeshTerms
Keywords
Journal Title the lancet. neurology
Publication Year Start




PMID- 29263008
OWN - NLM
STAT- MEDLINE
DCOM- 20171227
LR  - 20171227
IS  - 1474-4465 (Electronic)
IS  - 1474-4422 (Linking)
VI  - 17
IP  - 1
DP  - 2018 Jan
TI  - Investigating the genetic architecture of dementia with Lewy bodies: a two-stage 
      genome-wide association study.
PG  - 64-74
LID - S1474-4422(17)30400-3 [pii]
LID - 10.1016/S1474-4422(17)30400-3 [doi]
AB  - BACKGROUND: Dementia with Lewy bodies is the second most common form of dementia 
      in elderly people but has been overshadowed in the research field, partly because
      of similarities between dementia with Lewy bodies, Parkinson's disease, and
      Alzheimer's disease. So far, to our knowledge, no large-scale genetic study of
      dementia with Lewy bodies has been done. To better understand the genetic basis
      of dementia with Lewy bodies, we have done a genome-wide association study with
      the aim of identifying genetic risk factors for this disorder. METHODS: In this
      two-stage genome-wide association study, we collected samples from white
      participants of European ancestry who had been diagnosed with dementia with Lewy 
      bodies according to established clinical or pathological criteria. In the
      discovery stage (with the case cohort recruited from 22 centres in ten countries 
      and the controls derived from two publicly available database of Genotypes and
      Phenotypes studies [phs000404.v1.p1 and phs000982.v1.p1] in the USA), we
      performed genotyping and exploited the recently established Haplotype Reference
      Consortium panel as the basis for imputation. Pathological samples were
      ascertained following autopsy in each individual brain bank, whereas clinical
      samples were collected after participant examination. There was no specific
      timeframe for collection of samples. We did association analyses in all
      participants with dementia with Lewy bodies, and also only in participants with
      pathological diagnosis. In the replication stage, we performed genotyping of
      significant and suggestive results from the discovery stage. Lastly, we did a
      meta-analysis of both stages under a fixed-effects model and used logistic
      regression to test for association in each stage. FINDINGS: This study included
      1743 patients with dementia with Lewy bodies (1324 with pathological diagnosis)
      and 4454 controls (1216 patients with dementia with Lewy bodies vs 3791 controls 
      in the discovery stage; 527 vs 663 in the replication stage). Results confirm
      previously reported associations: APOE (rs429358; odds ratio [OR] 2.40, 95% CI
      2.14-2.70; p=1.05 x 10(-48)), SNCA (rs7681440; OR 0.73, 0.66-0.81; p=6.39 x
      10(-10)), an GBA (rs35749011; OR 2.55, 1.88-3.46; p=1.78 x 10(-9)). They also
      provide some evidence for a novel candidate locus, namely CNTN1 (rs7314908; OR
      1.51, 1.27-1.79; p=2.32 x 10(-6)); further replication will be important.
      Additionally, we estimate the heritable component of dementia with Lewy bodies to
      be about 36%. INTERPRETATION: Despite the small sample size for a genome-wide
      association study, and acknowledging the potential biases from ascertaining
      samples from multiple locations, we present the most comprehensive and well
      powered genetic study in dementia with Lewy bodies so far. These data show that
      common genetic variability has a role in the disease. FUNDING: The Alzheimer's
      Society and the Lewy Body Society.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Guerreiro, Rita
AU  - Guerreiro R
AD  - UK Dementia Research Institute, University College London, London, UK; Department
      of Molecular Neuroscience, UCL Institute of Neurology, University College London,
      London, UK; Department of Medical Sciences and Institute of Biomedicine, iBiMED, 
      University of Aveiro, Aveiro, Portugal.
FAU - Ross, Owen A
AU  - Ross OA
AD  - Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
FAU - Kun-Rodrigues, Celia
AU  - Kun-Rodrigues C
AD  - Department of Molecular Neuroscience, UCL Institute of Neurology, University
      College London, London, UK.
FAU - Hernandez, Dena G
AU  - Hernandez DG
AD  - Laboratory of Neurogenetics, National Institutes on Aging, National Institutes of
      Health, Bethesda, MD, USA; German Center for Neurodegenerative Diseases,
      Tubingen, Germany.
FAU - Orme, Tatiana
AU  - Orme T
AD  - Department of Molecular Neuroscience, UCL Institute of Neurology, University
      College London, London, UK.
FAU - Eicher, John D
AU  - Eicher JD
AD  - Merck & Co, Boston, MA, USA.
FAU - Shepherd, Claire E
AU  - Shepherd CE
AD  - Neuroscience Research Australia, Sydney, NSW, Australia; School of Medical
      Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW,
      Australia.
FAU - Parkkinen, Laura
AU  - Parkkinen L
AD  - Nuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre,
      University of Oxford, Oxford, UK.
FAU - Darwent, Lee
AU  - Darwent L
AD  - Department of Molecular Neuroscience, UCL Institute of Neurology, University
      College London, London, UK.
FAU - Heckman, Michael G
AU  - Heckman MG
AD  - Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL,
      USA.
FAU - Scholz, Sonja W
AU  - Scholz SW
AD  - Neurodegenerative Diseases Research Unit, National Institute of Neurological
      Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
FAU - Troncoso, Juan C
AU  - Troncoso JC
AD  - Department of Pathology (Neuropathology), Johns Hopkins University School of
      Medicine, Baltimore, MD, USA.
FAU - Pletnikova, Olga
AU  - Pletnikova O
AD  - Department of Pathology (Neuropathology), Johns Hopkins University School of
      Medicine, Baltimore, MD, USA.
FAU - Ansorge, Olaf
AU  - Ansorge O
AD  - Nuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre,
      University of Oxford, Oxford, UK.
FAU - Clarimon, Jordi
AU  - Clarimon J
AD  - Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i
      Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; Centro de
      Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED),
      Instituto de Salud Carlos III, Madrid, Spain.
FAU - Lleo, Alberto
AU  - Lleo A
AD  - Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i
      Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; Centro de
      Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED),
      Instituto de Salud Carlos III, Madrid, Spain.
FAU - Morenas-Rodriguez, Estrella
AU  - Morenas-Rodriguez E
AD  - Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i
      Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; Centro de
      Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED),
      Instituto de Salud Carlos III, Madrid, Spain.
FAU - Clark, Lorraine
AU  - Clark L
AD  - Taub Institute for Alzheimer Disease and the Aging Brain and Department of
      Pathology and Cell Biology, Columbia University, New York, NY, USA.
FAU - Honig, Lawrence S
AU  - Honig LS
AD  - Taub Institute for Alzheimer Disease and the Aging Brain and Department of
      Pathology and Cell Biology, Columbia University, New York, NY, USA.
FAU - Marder, Karen
AU  - Marder K
AD  - Taub Institute for Alzheimer Disease and the Aging Brain and Department of
      Pathology and Cell Biology, Columbia University, New York, NY, USA.
FAU - Lemstra, Afina
AU  - Lemstra A
AD  - Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU
      University Medical Center, Amsterdam, Netherlands.
FAU - Rogaeva, Ekaterina
AU  - Rogaeva E
AD  - Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto,
      ON, Canada; Department of Medicine, University of Toronto, ON, Canada.
FAU - St George-Hyslop, Peter
AU  - St George-Hyslop P
AD  - Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto,
      ON, Canada; Department of Medicine, University of Toronto, ON, Canada; Department
      of Clinical Neurosciences, Cambridge Institute for Medical Research, University
      of Cambridge, Cambridge, UK.
FAU - Londos, Elisabet
AU  - Londos E
AD  - Clinical Memory Research Unit, Institution of Clinical Sciences Malmo, Lund
      University, Sweden.
FAU - Zetterberg, Henrik
AU  - Zetterberg H
AD  - UK Dementia Research Institute, University College London, London, UK; Department
      of Molecular Neuroscience, UCL Institute of Neurology, University College London,
      London, UK; Clinical Neurochemistry Laboratory, Institute of Neuroscience and
      Physiology, Sahlgrenska Academy, University of Gothenburg, Molndal, Sweden.
FAU - Barber, Imelda
AU  - Barber I
AD  - Human Genetics, School of Life Sciences, Queens Medical Centre, University of
      Nottingham, Nottingham, UK.
FAU - Braae, Anne
AU  - Braae A
AD  - Human Genetics, School of Life Sciences, Queens Medical Centre, University of
      Nottingham, Nottingham, UK.
FAU - Brown, Kristelle
AU  - Brown K
AD  - Human Genetics, School of Life Sciences, Queens Medical Centre, University of
      Nottingham, Nottingham, UK.
FAU - Morgan, Kevin
AU  - Morgan K
AD  - Human Genetics, School of Life Sciences, Queens Medical Centre, University of
      Nottingham, Nottingham, UK.
FAU - Troakes, Claire
AU  - Troakes C
AD  - Department of Basic and Clinical Neuroscience and Institute of Psychiatry,
      Psychology and Neuroscience, King's College London, London, UK.
FAU - Al-Sarraj, Safa
AU  - Al-Sarraj S
AD  - Department of Basic and Clinical Neuroscience and Institute of Psychiatry,
      Psychology and Neuroscience, King's College London, London, UK.
FAU - Lashley, Tammaryn
AU  - Lashley T
AD  - Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of
      Neurology, University College London, London, UK.
FAU - Holton, Janice
AU  - Holton J
AD  - Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of
      Neurology, University College London, London, UK.
FAU - Compta, Yaroslau
AU  - Compta Y
AD  - Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of
      Neurology, University College London, London, UK; Parkinson's Disease & Movement 
      Disorders Unit, Neurology Service, Hospital Clinic, IDIBAPS, CIBERNED, Department
      of Biomedicine, University of Barcelona, Barcelona, Spain.
FAU - Van Deerlin, Vivianna
AU  - Van Deerlin V
AD  - Department of Pathology and Laboratory Medicine, Center for Neurodegenerative
      Disease Research, Perelman School of Medicine, University of Pennsylvania,
      Philadelphia, PA, USA.
FAU - Serrano, Geidy E
AU  - Serrano GE
AD  - Banner Sun Health Research Institute, Sun City, AZ, USA.
FAU - Beach, Thomas G
AU  - Beach TG
AD  - Banner Sun Health Research Institute, Sun City, AZ, USA.
FAU - Lesage, Suzanne
AU  - Lesage S
AD  - Inserm U1127, CNRS UMR7225, Sorbonne Universites, UPMC Univ Paris 06, UMR, Paris,
      France; S1127, Institut du Cerveau et de la Moelle epiniere, Paris, France.
FAU - Galasko, Douglas
AU  - Galasko D
AD  - Department of Neurosciences, University of California, San Diego, La Jolla, CA,
      USA; Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA.
FAU - Masliah, Eliezer
AU  - Masliah E
AD  - Laboratory of Neurogenetics, National Institutes on Aging, National Institutes of
      Health, Bethesda, MD, USA; Division of Neurosciences, National Institutes of
      Health, Bethesda, MD, USA.
FAU - Santana, Isabel
AU  - Santana I
AD  - Neurology Service, University of Coimbra Hospital, Coimbra, Portugal.
FAU - Pastor, Pau
AU  - Pastor P
AD  - Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas
      (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain; Memory Unit, Department
      of Neurology, University Hospital Mutua de Terrassa, University of Barcelona,
      Barcelona, Spain; Fundacio de Docencia I Recerca Mutua de Terrassa, Terrassa,
      Barcelona, Spain.
FAU - Diez-Fairen, Monica
AU  - Diez-Fairen M
AD  - Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas
      (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain; Memory Unit, Department
      of Neurology, University Hospital Mutua de Terrassa, University of Barcelona,
      Barcelona, Spain; Fundacio de Docencia I Recerca Mutua de Terrassa, Terrassa,
      Barcelona, Spain.
FAU - Aguilar, Miquel
AU  - Aguilar M
AD  - Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas
      (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain; Memory Unit, Department
      of Neurology, University Hospital Mutua de Terrassa, University of Barcelona,
      Barcelona, Spain; Fundacio de Docencia I Recerca Mutua de Terrassa, Terrassa,
      Barcelona, Spain.
FAU - Tienari, Pentti J
AU  - Tienari PJ
AD  - Molecular Neurology, Research Programs Unit, University of Helsinki, Helsinki,
      Finland; Department of Neurology, Helsinki University Hospital, Helsinki,
      Finland.
FAU - Myllykangas, Liisa
AU  - Myllykangas L
AD  - Department of Pathology, Haartman Institute, University of Helsinki, Helsinki,
      Finland; HUSLAB, Helsinki, Finland.
FAU - Oinas, Minna
AU  - Oinas M
AD  - Department of Neurosurgery, University of Helsinki, Helsinki, Finland; Department
      of Neuropathology and Neurosurgery, Helsinki University Hospital, Helsinki,
      Finland.
FAU - Revesz, Tamas
AU  - Revesz T
AD  - Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of
      Neurology, University College London, London, UK.
FAU - Lees, Andrew
AU  - Lees A
AD  - Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of
      Neurology, University College London, London, UK.
FAU - Boeve, Brad F
AU  - Boeve BF
AD  - Department of Neurology, Mayo Clinic, Rochester, MN, USA.
FAU - Petersen, Ronald C
AU  - Petersen RC
AD  - Department of Neurology, Mayo Clinic, Rochester, MN, USA.
FAU - Ferman, Tanis J
AU  - Ferman TJ
AD  - Department of Psychiatry, Mayo Clinic, Jacksonville, FL, USA.
FAU - Escott-Price, Valentina
AU  - Escott-Price V
AD  - MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine,
      Cardiff University, Cardiff, UK.
FAU - Graff-Radford, Neill
AU  - Graff-Radford N
AD  - Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
FAU - Cairns, Nigel J
AU  - Cairns NJ
AD  - Knight Alzheimer's Disease Research Center, Department of Neurology, Washington
      University School of Medicine, Saint Louis, MO, USA.
FAU - Morris, John C
AU  - Morris JC
AD  - Knight Alzheimer's Disease Research Center, Department of Neurology, Washington
      University School of Medicine, Saint Louis, MO, USA.
FAU - Pickering-Brown, Stuart
AU  - Pickering-Brown S
AD  - Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human
      Sciences, University of Manchester, Manchester, UK.
FAU - Mann, David
AU  - Mann D
AD  - Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human
      Sciences, University of Manchester, Manchester, UK.
FAU - Halliday, Glenda M
AU  - Halliday GM
AD  - Neuroscience Research Australia, Sydney, NSW, Australia; School of Medical
      Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW,
      Australia; Brain and Mind Centre, Sydney Medical School, University of Sydney,
      Sydney, NSW, Australia.
FAU - Hardy, John
AU  - Hardy J
AD  - UK Dementia Research Institute, University College London, London, UK; Department
      of Molecular Neuroscience, UCL Institute of Neurology, University College London,
      London, UK.
FAU - Trojanowski, John Q
AU  - Trojanowski JQ
AD  - Department of Pathology and Laboratory Medicine, Center for Neurodegenerative
      Disease Research, Perelman School of Medicine, University of Pennsylvania,
      Philadelphia, PA, USA.
FAU - Dickson, Dennis W
AU  - Dickson DW
AD  - Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
FAU - Singleton, Andrew
AU  - Singleton A
AD  - Laboratory of Neurogenetics, National Institutes on Aging, National Institutes of
      Health, Bethesda, MD, USA.
FAU - Stone, David J
AU  - Stone DJ
AD  - Merck & Co, West Point, PA, USA.
FAU - Bras, Jose
AU  - Bras J
AD  - UK Dementia Research Institute, University College London, London, UK; Department
      of Molecular Neuroscience, UCL Institute of Neurology, University College London,
      London, UK; Department of Medical Sciences and Institute of Biomedicine, iBiMED, 
      University of Aveiro, Aveiro, Portugal. Electronic address: [email protected]
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20171216
PL  - England
TA  - Lancet Neurol
JT  - The Lancet. Neurology
JID - 101139309
SB  - IM
MH  - Cohort Studies
MH  - Genome-Wide Association Study/*methods
MH  - Humans
MH  - Lewy Body Disease/*genetics
EDAT- 2017/12/22 06:00
MHDA- 2017/12/28 06:00
CRDT- 2017/12/22 06:00
PHST- 2017/06/21 00:00 [received]
PHST- 2017/08/17 00:00 [revised]
PHST- 2017/11/03 00:00 [accepted]
PHST- 2017/12/22 06:00 [entrez]
PHST- 2017/12/22 06:00 [pubmed]
PHST- 2017/12/28 06:00 [medline]
AID - S1474-4422(17)30400-3 [pii]
AID - 10.1016/S1474-4422(17)30400-3 [doi]
PST - ppublish
SO  - Lancet Neurol. 2018 Jan;17(1):64-74. doi: 10.1016/S1474-4422(17)30400-3. Epub
      2017 Dec 16.