Heritability and genetic variance of dementia with Lewy bodies

Rita Guerreiro; Valentina Escott-Price; Dena Hernandez; Celia Kun-Rodrigues; Owen Ross; Tatiana Orme; Joao Luis Neto; Susana Carmona; Nadia Dehghani; John Eicher; Claire Shepherd; Laura Parkkinen; Lee Darwent; Michael Heckman; Sonja Scholz; Juan Troncoso; Olga Pletnikova; Ted Dawson; Liana Rosenthal; Olaf Ansorge; Jordi Clarimon; Alberto Lleo; Estrella Morenas-Rodriguez; Lorraine Clark; Lawrence Honig; Karen Marder; Afina Lemstra; Ekaterina Rogaeva; Peter St George-Hyslop; Elisabet Londos; Henrik Zetterberg; Imelda Barber; Anne Braae; Kristelle Brown; Kevin Morgan; Claire Troakes; Safa Al-Sarraj; Tammaryn Lashley; Janice Holton; Yaroslau Compta; Vivianna van Deerlin; Geidy Serrano; Thomas Beach; Suzanne Lesage; Douglas Galasko; Eliezer Masliah; Isabel Santana; Pau Pastor; Monica Diez-Fairen; Miquel Aguilar; Pentti Tienari; Liisa Myllykangas; Minna Oinas; Tamas Revesz; Andrew Lees; Brad Boeve; Ronald Petersen; Tanis Ferman; Neill Graff-Radford; Nigel Cairns; John Morris; Stuart Pickering-Brown; David Mann; Glenda Halliday; John Hardy; John Trojanowski; Dennis Dickson; Andrew Singleton; David Stone; Jose Bras; Peter St. George-Hyslop

doi:10.1016/j.nbd.2019.04.004

Journal Articles Neurobiology of Disease Year : 2019

Heritability and genetic variance of dementia with Lewy bodies

(1) , (2) , (3) , (1) , (4) , (1) , (1) , (1) , (1) , (1, 5) , (6) , (7) , (2) , (4) , (8, 9) , (9) , (9) , (9) , (9) , (7) , (10, 11) , (10, 11) , (10, 11, 12) , (13) , (13) , (13) , (14) , (15, 16) , (15, 16, 17) , (18) , (2, 19) , (20) , (20) , (20) , (20) , (21) , (21) , (22) , (22) , (22, 23) , (24) , , , (25) , , , , , , , , , , , , , , , , , , , , , , (24) , , , , ,

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25

Rita Guerreiro

Function : Author

UCL Institute of Neurology, Queen Square [London]

Valentina Escott-Price

Function : Author
PersonId : 1305604
ORCID : 0000-0003-1784-5483

UK Dementia Research Institute

Dena Hernandez

Function : Author

National Institute on Aging [Bethesda, USA]

Celia Kun-Rodrigues

Function : Author

UCL Institute of Neurology, Queen Square [London]

Owen Ross

Function : Author

Mayo Clinic [Jacksonville]

Tatiana Orme

Function : Author

UCL Institute of Neurology, Queen Square [London]

Joao Luis Neto

Function : Author

UCL Institute of Neurology, Queen Square [London]

Susana Carmona

Function : Author

UCL Institute of Neurology, Queen Square [London]

Nadia Dehghani

Function : Author

UCL Institute of Neurology, Queen Square [London]

John Eicher

Function : Author

UCL Institute of Neurology, Queen Square [London]

Merck Research Laboratories

Claire Shepherd

Function : Author

University of New South Wales [Sydney]

Laura Parkkinen

Function : Author

Nuffield Department of Clinical Neurosciences [Oxford]

Lee Darwent

Function : Author

UK Dementia Research Institute

Michael Heckman

Function : Author

Mayo Clinic [Jacksonville]

Sonja Scholz

Function : Author

National Institute of Neurological Disorders and Stroke [Bethesda]

Johns Hopkins University School of Medicine [Baltimore]

Juan Troncoso

Function : Author

Johns Hopkins University School of Medicine [Baltimore]

Olga Pletnikova

Function : Author

Johns Hopkins University School of Medicine [Baltimore]

Ted Dawson

Function : Author

Johns Hopkins University School of Medicine [Baltimore]

Liana Rosenthal

Function : Author

Johns Hopkins University School of Medicine [Baltimore]

Olaf Ansorge

Function : Author

Nuffield Department of Clinical Neurosciences [Oxford]

Jordi Clarimon

Function : Author

Hospital de la Santa Creu i Sant Pau

Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona

Alberto Lleo

Function : Author

Hospital de la Santa Creu i Sant Pau

Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona

Estrella Morenas-Rodriguez

Function : Author

Hospital de la Santa Creu i Sant Pau

Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona

Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas

Lorraine Clark

Function : Author

Columbia University [New York]

Lawrence Honig

Function : Author

Columbia University [New York]

Karen Marder

Function : Author

Columbia University [New York]

Afina Lemstra

Function : Author

VU University Medical Center [Amsterdam]

Ekaterina Rogaeva

Function : Author

Tanz Center Research in Neurodegenerative Diseases [Toronto]

University of Toronto

Peter St George-Hyslop

Function : Author

Tanz Center Research in Neurodegenerative Diseases [Toronto]

University of Toronto

Cambridge Institute for Medical Research

Elisabet Londos

Function : Author

Lund University

Henrik Zetterberg

Function : Author

UK Dementia Research Institute

Sahlgrenska Academy at University of Gothenburg [Göteborg]

Imelda Barber

Function : Author

University of Nottingham, UK

Anne Braae

Function : Author

University of Nottingham, UK

Kristelle Brown

Function : Author

University of Nottingham, UK

Kevin Morgan

Function : Author

University of Nottingham, UK

Claire Troakes

Function : Author

King‘s College London

Safa Al-Sarraj

Function : Author

King‘s College London

Tammaryn Lashley

Function : Author

UCL Queen Square Institute of Neurology

Janice Holton

Function : Author

UCL Queen Square Institute of Neurology

Yaroslau Compta

Function : Author

UCL Queen Square Institute of Neurology

Institut d'Investigacions Biomèdiques August Pi i Sunyer

Vivianna van Deerlin

Function : Author

Perelman School of Medicine

Geidy Serrano

Function : Author

Thomas Beach

Function : Author

Suzanne Lesage

Function : Author

Institut du Cerveau = Paris Brain Institute

Douglas Galasko

Function : Author

Eliezer Masliah

Function : Author

Isabel Santana

Function : Author

Pau Pastor

Function : Author
PersonId : 1377660
ORCID : 0000-0002-2573-6378

Monica Diez-Fairen

Function : Author

Miquel Aguilar

Function : Author

Pentti Tienari

Function : Author

Liisa Myllykangas

Function : Author

Minna Oinas

Function : Author

Tamas Revesz

Function : Author

Andrew Lees

Function : Author

Brad Boeve

Function : Author

Ronald Petersen

Function : Author

Tanis Ferman

Function : Author

Neill Graff-Radford

Function : Author

Nigel Cairns

Function : Author

John Morris

Function : Author

Stuart Pickering-Brown

Function : Author

David Mann

Function : Author

Glenda Halliday

Function : Author

John Hardy

Function : Author

John Trojanowski

Function : Author

Perelman School of Medicine

Dennis Dickson

Function : Author

Andrew Singleton

Function : Author

David Stone

Function : Author

Jose Bras

Function : Author
PersonId : 1359609
ORCID : 0000-0001-8186-0333

Peter St. George-Hyslop

Function : Author

Abstract

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.

Keywords

Dementia Genetic correlation Genetic variance Lewy bodies

Domains

Life Sciences [q-bio]

Gestionnaire HAL 4 Sorbonne Université : Connect in order to contact the contributor

https://hal.sorbonne-universite.fr/hal-04560893

Submitted on : Friday, April 26, 2024-3:27:00 PM

Last modification on : Friday, November 22, 2024-3:44:02 PM

Dates and versions

hal-04560893 , version 1 (26-04-2024)

Identifiers

HAL Id : hal-04560893 , version 1
DOI : 10.1016/j.nbd.2019.04.004
PUBMED : 30953760
PUBMEDCENTRAL : PMC6588425

Cite

Rita Guerreiro, Valentina Escott-Price, Dena Hernandez, Celia Kun-Rodrigues, Owen Ross, et al.. Heritability and genetic variance of dementia with Lewy bodies. Neurobiology of Disease, 2019, 127, pp.492-501. ⟨10.1016/j.nbd.2019.04.004⟩. ⟨hal-04560893⟩

Export

BibTeX XML-TEI Dublin Core DC Terms EndNote DataCite

Collections

CNRS ICM SORBONNE-UNIVERSITE SU-MEDECINE ANR

13 View

0 Download

Heritability and genetic variance of dementia with Lewy bodies

Abstract

Keywords

Domains

Dates and versions

Identifiers

Cite

Export

Collections

Altmetric

Share