Heritability and genetic variance of dementia with Lewy bodies.

Databases, Genetic Genetic Predisposition to Disease Genetic Variation Humans Lewy Body Disease / genetics
Dementia Genetic correlation Genetic variance Lewy bodies

Journal

Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169

Informations de publication

Date de publication:
07 2019
Historique:
received: 02 01 2019
revised: 23 03 2019
accepted: 02 04 2019
pubmed: 7 4 2019
medline: 10 1 2020
entrez: 7 4 2019
Statut: ppublish

Résumé

Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson's disease (PD) or Alzheimer's disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.

Identifiants

DOI: 10.1016/j.nbd.2019.04.004 PMID: 30953760 PMC: PMC6588425
pubmed: 30953760
pii: S0969-9961(19)30095-6
doi: 10.1016/j.nbd.2019.04.004
pmc: PMC6588425
mid: NIHMS1526803
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

492-501

Subventions

Organisme : Medical Research Council
ID : MR/K01417X/1
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : P50 NS053488
Pays : United States
Organisme : Parkinson's UK
ID : J-0804
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG033193
Pays : United States
Organisme : FIC NIH HHS
ID : R03 TW008019
Pays : United States
Organisme : Medical Research Council
ID : MR/J004758/1
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : ZIA NS003154
Pays : United States
Organisme : NINDS NIH HHS
ID : P50 NS038377
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG048349
Pays : United States
Organisme : Medical Research Council
ID : G0901254
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : P50 NS071674
Pays : United States
Organisme : Medical Research Council
ID : MR/L022656/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG010124
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA NS003154-01
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 AG000951
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS078086
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004446
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA AG000951-12
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS100600
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005131
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NINDS NIH HHS
ID : P50 NS038370
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016574
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA141668
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005146
Pays : United States
Organisme : Medical Research Council
ID : G1001253
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG032984
Pays : United States
Organisme : Medical Research Council
ID : MR/L016397/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L501542/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P50 AG008702
Pays : United States
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : Z01 ES101986
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA089392
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG003991
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005681
Pays : United States
Organisme : Medical Research Council
ID : G1001799
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P01 AG014248
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062429
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NIDA NIH HHS
ID : P50 DA019706
Pays : United States
Organisme : Medical Research Council
ID : MR/N026004/1
Pays : United Kingdom
Organisme : Parkinson's UK
ID : G-1307
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : HHSN268200782096C
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA084724
Pays : United States
Organisme : Medical Research Council
ID : G1100540
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : Z01 AG000949
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS060113
Pays : United States
Organisme : Medical Research Council
ID : G0900652
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : P50 NS072187
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG004953
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS110435
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS037167
Pays : United States
Organisme : Parkinson's UK
ID : J-0901
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400074
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : UL1 TR000040
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0701075
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG006786
Pays : United States
Organisme : Medical Research Council
ID : G0502157
Pays : United Kingdom

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Références

Am J Hum Genet. 2011 Mar 11;88(3):294-305
pubmed: 21376301
Nat Genet. 2015 Nov;47(11):1236-41
pubmed: 26414676
Immunology. 2016 Dec;149(4):423-431
pubmed: 27502741
Mol Psychiatry. 2014 Feb;19(2):253-8
pubmed: 23358156
Lancet Neurol. 2011 Sep;10(9):819-28
pubmed: 21775213
Lancet Neurol. 2018 Jan;17(1):64-74
pubmed: 29263008
J Neurol Sci. 2005 Dec 15;239(1):45-52
pubmed: 16225890
Am J Hum Genet. 2011 Jan 7;88(1):76-82
pubmed: 21167468
Hum Mol Genet. 2014 Dec 1;23(23):6139-46
pubmed: 24973356
Lancet Neurol. 2014 Aug;13(8):788-94
pubmed: 25030513
PLoS Genet. 2013;9(3):e1003355
pubmed: 23505390
Neurobiol Aging. 2016 Feb;38:214.e7-214.e10
pubmed: 26643944
Nat Genet. 2014 Sep;46(9):989-93
pubmed: 25064009
Ann Neurol. 2015 Apr;77(4):582-91
pubmed: 25773351
Nat Genet. 2013 Dec;45(12):1452-8
pubmed: 24162737
PLoS Med. 2017 Jun 13;14(6):e1002314
pubmed: 28609445
Am J Hum Genet. 2017 Jul 6;101(1):5-22
pubmed: 28686856
Nat Rev Genet. 2010 Jun;11(6):446-50
pubmed: 20479774
Nat Genet. 2015 Oct;47(10):1114-20
pubmed: 26323059
Nat Commun. 2018 Jan 30;9(1):327
pubmed: 29382830
Annu Rev Genet. 2001;35:303-39
pubmed: 11700286
Nat Genet. 2016 Oct;48(10):1279-83
pubmed: 27548312
Am J Hum Genet. 2015 Mar 5;96(3):377-85
pubmed: 25683123
Bioinformatics. 2015 May 1;31(9):1466-8
pubmed: 25550326
JAMA Neurol. 2013 Jun;70(6):727-35
pubmed: 23588557
Cell. 2017 Jun 15;169(7):1177-1186
pubmed: 28622505
Neurosci Lett. 1994 Nov 21;182(1):1-2
pubmed: 7891871
Bioinformatics. 2017 Jan 15;33(2):272-279
pubmed: 27663502
Nature. 2016 May 11;533(7604):539-42
pubmed: 27225129
Hum Mol Genet. 2014 Sep 15;23(R1):R47-53
pubmed: 24794858
Brain. 2015 Dec;138(Pt 12):3673-84
pubmed: 26490334
Nature. 2015 Apr 9;520(7546):224-9
pubmed: 25607358
Nature. 2009 Oct 8;461(7265):747-53
pubmed: 19812666
Nat Commun. 2016 Mar 23;7:11122
pubmed: 27005778
Bioinformatics. 2012 Oct 1;28(19):2540-2
pubmed: 22843982

Auteurs

Rita Guerreiro (R)

Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK; UK Dementia Research Institute (UK DRI) at UCL, London, UK.

Valentina Escott-Price (V)

UK Dementia Research Institute (UK DRI) at Cardiff, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.

Dena G Hernandez (DG)

Laboratory of Neurogenetics, National Institutes on Aging, NIH, Bethesda, MD, USA; German Center for Neurodegenerative Diseases (DZNE)-Tubingen, Germany.

Celia Kun-Rodrigues (C)

Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK.

Owen A Ross (OA)

Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.

Tatiana Orme (T)

Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK; UK Dementia Research Institute (UK DRI) at UCL, London, UK.

Joao Luis Neto (JL)

Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK; UK Dementia Research Institute (UK DRI) at UCL, London, UK.

Susana Carmona (S)

Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK; UK Dementia Research Institute (UK DRI) at UCL, London, UK.

Nadia Dehghani (N)

Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK; UK Dementia Research Institute (UK DRI) at UCL, London, UK.

John D Eicher (JD)

Genetics and Pharmacogenomics, Merck Research Laboratories, Boston, MA, USA.

Claire Shepherd (C)

Neuroscience Research Australia, Sydney, Australia and School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.

Laura Parkkinen (L)

Nuffield Department of Clinical Neurosciences, Oxford Parkinsons Disease Centre, University of Oxford, Oxford, UK.

Lee Darwent (L)

UK Dementia Research Institute (UK DRI) at UCL, London, UK.

Michael G Heckman (MG)

Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, USA.

Sonja W Scholz (SW)

Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Juan C Troncoso (JC)

Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Olga Pletnikova (O)

Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Ted Dawson (T)

Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Liana Rosenthal (L)

Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Olaf Ansorge (O)

Nuffield Department of Clinical Neurosciences, Oxford Parkinsons Disease Centre, University of Oxford, Oxford, UK.

Jordi Clarimon (J)

Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.

Alberto Lleo (A)

Memory Unit, Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.

Estrella Morenas-Rodriguez (E)

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.

Lorraine Clark (L)

Taub Institute for Alzheimer Disease and the Aging Brain, Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.

Lawrence S Honig (LS)

Taub Institute for Alzheimer Disease and the Aging Brain, Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.

Karen Marder (K)

Taub Institute for Alzheimer Disease and the Aging Brain, Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.

Afina Lemstra (A)

Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.

Ekaterina Rogaeva (E)

Tanz Centre for Research in Neurodegenerative Diseases and department of Medicine, University of Toronto, Ontario, Canada.

Peter St George-Hyslop (P)

Tanz Centre for Research in Neurodegenerative Diseases and department of Medicine, University of Toronto, Ontario, Canada; Department of Clinical Neurosciences, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.

Elisabet Londos (E)

Clinical Memory Research Unit, Institution of Clinical Sciences Malmo, Lund University, Sweden.

Henrik Zetterberg (H)

UK Dementia Research Institute at UCL, London UK, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden.

Imelda Barber (I)

Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.

Anne Braae (A)

Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.

Kristelle Brown (K)

Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.

Kevin Morgan (K)

Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.

Claire Troakes (C)

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.

Safa Al-Sarraj (S)

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.

Tammaryn Lashley (T)

Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.

Janice Holton (J)

Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.

Yaroslau Compta (Y)

Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK, Movement Disorders Unit, Neurology Service, Clinical Neuroscience Institute (ICN), Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Catalonia, Spain.

Vivianna Van Deerlin (V)

Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, 3600 Spruce Street, Philadelphia, USA.

Geidy E Serrano (GE)

Banner Sun Health Research Institute, 10515 W Santa Fe Drive, Sun City, AZ 85351, USA.

Thomas G Beach (TG)

Banner Sun Health Research Institute, 10515 W Santa Fe Drive, Sun City, AZ 85351, USA.

Suzanne Lesage (S)

Inserm U1127, CNRS UMR7225, Sorbonne Universites, UPMC Univ Paris 06, UMR and S1127, Institut du Cerveau et de la Moelle epiniere, Paris, France.

Douglas Galasko (D)

Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States, Veterans Affairs San Diego Healthcare System, La Jolla, CA, United States.

Eliezer Masliah (E)

Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States, Department of Pathology, University of California, San Diego, La Jolla, CA, United States.

Isabel Santana (I)

Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Faculty of Medicine and Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.

Pau Pastor (P)

Memory Unit, Department of Neurology,University Hospital Mutua de Terrassa, University of Barcelona, Fundacion de Docencia I Recerca Mutua de Terrassa, Terrassa, Barcelona, Spain. Centro de Investigacion Biomedica en Red Enfermedades Neurdegenerativas (CIBERNED), Madrid, Spain.

Monica Diez-Fairen (M)

Memory Unit, Department of Neurology,University Hospital Mutua de Terrassa, University of Barcelona, Fundacion de Docencia I Recerca Mutua de Terrassa, Terrassa, Barcelona, Spain. Centro de Investigacion Biomedica en Red Enfermedades Neurdegenerativas (CIBERNED), Madrid, Spain.

Miquel Aguilar (M)

Memory Unit, Department of Neurology,University Hospital Mutua de Terrassa, University of Barcelona, Fundacion de Docencia I Recerca Mutua de Terrassa, Terrassa, Barcelona, Spain. Centro de Investigacion Biomedica en Red Enfermedades Neurdegenerativas (CIBERNED), Madrid, Spain.

Pentti J Tienari (PJ)

Molecular Neurology, Research Programs Unit, University of Helsinki, Department of Neurology, Helsinki University Hospital, Helsinki, Finland.

Liisa Myllykangas (L)

Department of Pathology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

Minna Oinas (M)

Department of Neuropathology and Neurosurgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

Tamas Revesz (T)

Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.

Andrew Lees (A)

Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.

Brad F Boeve (BF)

Neurology Department, Mayo Clinic, Rochester, MN, USA.

Ronald C Petersen (RC)

Neurology Department, Mayo Clinic, Rochester, MN, USA.

Tanis J Ferman (TJ)

Department of Psychiatry and Department of Psychology, Mayo Clinic, Jacksonville, FL, USA.

Neill Graff-Radford (N)

Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.

Nigel J Cairns (NJ)

Knight Alzheimers Disease Research Center, Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.

John C Morris (JC)

Knight Alzheimers Disease Research Center, Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.

Stuart Pickering-Brown (S)

Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.

David Mann (D)

Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.

Glenda M Halliday (GM)

Neuroscience Research Australia, Sydney, Australia and School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia; Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, Australia.

John Hardy (J)

Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK.

John Q Trojanowski (JQ)

Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, 3600 Spruce Street, Philadelphia, USA.

Dennis W Dickson (DW)

Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.

Andrew Singleton (A)

Laboratory of Neurogenetics, National Institutes on Aging, NIH, Bethesda, MD, USA.

David J Stone (DJ)

Genetics and Pharmacogenomics, Merck Research Laboratories, West Point, PA, USA.

Jose Bras (J)

Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK; UK Dementia Research Institute (UK DRI) at UCL, London, UK. Electronic address: j.bras@ucl.ac.uk.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Sciences de l'information › Mémorisation et recherche des informations › Bases de données comme sujet › Bases de données factuelles › Bases de données génétiques › Heritability and genetic variance of dementia...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Heritability and genetic variance of dementia...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Heritability and genetic variance of dementia...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Heritability and genetic variance of dementia...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie à corps de Lewy › Heritability and genetic variance of dementia...