Evidence map›Paper›PMID 29263008›Full record

ArticleThe Lancet. Neurology2018

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

Rita Guerreiro, Owen A Ross, Celia Kun-Rodrigues, Dena G Hernandez, Tatiana Orme, John D Eicher, Claire E Shepherd, Laura Parkkinen, Lee Darwent, Michael G Heckman and 55 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
183citing papers in PubMed, 6 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

183 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. Pooled it
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  6. Effect of GBA gene variants on clinical characteristics of dementia with Lewy bodies: a review and meta-analyses.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022
    Pooled it
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  16. Where do PDD and DLB SYNdromes fit in neuronal alpha-SYNuclein biological frameworks?Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  17. Article
  18. Article
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  20. Heterogeneity of dementia with lewy bodies: Insights from clinical presentations, neuropathology, and biomarkers.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Review

123 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

65 authors.

Rita GuerreiroUK 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.
Owen A RossDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Celia Kun-RodriguesDepartment of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
Dena G HernandezLaboratory of Neurogenetics, National Institutes on Aging, National Institutes of Health, Bethesda, MD, USA; German Center for Neurodegenerative Diseases, Tubingen, Germany.
Tatiana OrmeDepartment of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
John D EicherMerck & Co, Boston, MA, USA.
Claire E ShepherdNeuroscience Research Australia, Sydney, NSW, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Laura ParkkinenNuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK.
Lee DarwentDepartment of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
Michael G HeckmanDivision of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, USA.
Sonja W ScholzNeurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Juan C TroncosoDepartment of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Olga PletnikovaDepartment of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Olaf AnsorgeNuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK.
Jordi ClarimonMemory 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.
Alberto LleoMemory 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.
Estrella Morenas-RodriguezMemory 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.
Lorraine ClarkTaub Institute for Alzheimer Disease and the Aging Brain and Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Lawrence S HonigTaub Institute for Alzheimer Disease and the Aging Brain and Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Karen MarderTaub Institute for Alzheimer Disease and the Aging Brain and Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Afina LemstraDepartment of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
Ekaterina RogaevaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, ON, Canada; Department of Medicine, University of Toronto, ON, Canada.
Peter St George-HyslopTanz 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.
Elisabet LondosClinical Memory Research Unit, Institution of Clinical Sciences Malmo, Lund University, Sweden.
Henrik ZetterbergUK 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.
Imelda BarberHuman Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
Anne BraaeHuman Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
Kristelle BrownHuman Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
Kevin MorganHuman Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
Claire TroakesDepartment of Basic and Clinical Neuroscience and Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Safa Al-SarrajDepartment of Basic and Clinical Neuroscience and Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Tammaryn LashleyQueen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
Janice HoltonQueen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
Yaroslau ComptaQueen 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.
Vivianna Van DeerlinDepartment of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Geidy E SerranoBanner Sun Health Research Institute, Sun City, AZ, USA.
Thomas G BeachBanner Sun Health Research Institute, Sun City, AZ, USA.
Suzanne LesageInserm U1127, CNRS UMR7225, Sorbonne Universites, UPMC Univ Paris 06, UMR, Paris, France; S1127, Institut du Cerveau et de la Moelle epiniere, Paris, France.
Douglas GalaskoDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA.
Eliezer MasliahLaboratory of Neurogenetics, National Institutes on Aging, National Institutes of Health, Bethesda, MD, USA; Division of Neurosciences, National Institutes of Health, Bethesda, MD, USA.
Isabel SantanaNeurology Service, University of Coimbra Hospital, Coimbra, Portugal.
Pau PastorCentro 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.
Monica Diez-FairenCentro 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.
Miquel AguilarCentro 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.
Pentti J TienariMolecular Neurology, Research Programs Unit, University of Helsinki, Helsinki, Finland; Department of Neurology, Helsinki University Hospital, Helsinki, Finland.
Liisa MyllykangasDepartment of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland; HUSLAB, Helsinki, Finland.
Minna OinasDepartment of Neurosurgery, University of Helsinki, Helsinki, Finland; Department of Neuropathology and Neurosurgery, Helsinki University Hospital, Helsinki, Finland.
Tamas ReveszQueen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
Andrew LeesQueen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
Brad F BoeveDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Tanis J FermanDepartment of Psychiatry, Mayo Clinic, Jacksonville, FL, USA.
Valentina Escott-PriceMRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
Neill Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Nigel J CairnsKnight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.
John C MorrisKnight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.
Stuart Pickering-BrownInstitute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
David MannInstitute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
Glenda M HallidayNeuroscience 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.
John HardyUK Dementia Research Institute, University College London, London, UK; Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
John Q TrojanowskiDepartment of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Andrew SingletonLaboratory of Neurogenetics, National Institutes on Aging, National Institutes of Health, Bethesda, MD, USA.
David J StoneMerck & Co, West Point, PA, USA.
Jose BrasUK 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: j.bras@ucl.ac.uk.

Funding

VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
Understanding Mechanisms of a-synuclein pathologyP50NS038377 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KO, HANSEOK · 1998 to 2019
$38.8M
'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI HUGANIR, RICHARD L · 1985 to 2019
$37.6M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI BU, GUOJUN · 1999 to 2018
$36.9M
UPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI XIE, SHARON XIANGWEN · 1991 to 2020
$35.1M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
TRANSLATIONAL APPROACHES TO NEUROPROTECTION OF AXONS IN PDrP50NS038370 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BURKE, ROBERT E · 1999 to 2014
$24.0M
Project IV: "Alpha-Synuclein Strains & Diverse Synucleinopathies"P50NS053488 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI TROJANOWSKI, JOHN Q. · 2007 to 2017
$20.9M
The Collaborative Genetic Study of Nicotine DependenceP01CA089392 · NCI · WASHINGTON UNIVERSITY · PI BIERUT, LAURA J. · 2001 to 2012
$17.3M
Genetic characterization of atypical parkinsonismZIANS003154 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI SCHOLZ, SONJA · 2016 to 2025
$15.4M
Alzheimer's Society 200Intramural NIH HHS Z01 AG000951Intramural NIH HHS ZIA AG000951Intramural NIH HHS ZIA NS003154Medical Research Council G0400074Medical Research Council G0502157Medical Research Council G0900652Medical Research Council G1100540Medical Research Council MC_G1000734Medical Research Council MR/L010305/1Medical Research Council MR/L016397/1Medical Research Council MR/L022656/1Medical Research Council MR/L023784/1Medical Research Council MR/L023784/2Medical Research Council MR/N012453/1Medical Research Council MR/P005748/1NCATS NIH HHS UL1 TR000040NCI NIH HHS P01 CA089392NCI NIH HHS P50 CA084724NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01 HG004446NIAMS NIH HHS R01 AR042742NIA NIH HHS P30 AG010124NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016574NIA NIH HHS U01 AG006786NIDA NIH HHS P50 DA019706NINDS NIH HHS P50 NS038370NINDS NIH HHS P50 NS038377NINDS NIH HHS P50 NS053488NINDS NIH HHS P50 NS072187NINDS NIH HHS R01 NS060113NINDS NIH HHS R01 NS078086NINDS NIH HHS U01 NS100600Wellcome Trust 203249/Z/16/Z
6 · The paper itself

Abstract

backgroundDementia 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.

methodsIn 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.

findingsThis 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 × 10

interpretationDespite 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.

fundingThe Alzheimer's Society and the Lewy Body Society.

Indexed as

Cohort StudiesGenome-Wide Association StudyHumansLewy Body Disease

Identifiers

PMID29263008
PMCPMC5805394

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