Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
Ruth Chia
,
Marya Sabir
,
Sara Bandres-Ciga
,
Sara Saez-Atienzar
,
Regina Reynolds
,
Emil Gustavsson
,
Ronald Walton
,
Sarah Ahmed
,
Coralie Viollet
,
Jinhui Ding
,
Mary Makarious
,
Monica Diez-Fairen
,
Makayla Portley
,
Zalak Shah
,
Yevgeniya Abramzon
,
Dena Hernandez
,
Cornelis Blauwendraat
,
David Stone
,
John Eicher
,
Laura Parkkinen
,
Olaf Ansorge
,
Lorraine Clark
,
Lawrence Honig
,
Karen Marder
,
Afina Lemstra
,
Peter St George-Hyslop
,
Elisabet Londos
,
Kevin Morgan
,
Tammaryn Lashley
,
Thomas Warner
,
Zane Jaunmuktane
,
Douglas Galasko
,
Isabel Santana
,
Pentti Tienari
,
Liisa Myllykangas
,
Minna Oinas
,
Nigel Cairns
,
John Morris
,
Glenda Halliday
,
Vivianna van Deerlin
,
John Trojanowski
,
Maurizio Grassano
,
Andrea Calvo
,
Gabriele Mora
,
Antonio Canosa
,
Gianluca Floris
,
Ryan Bohannan
,
Francesca Brett
,
Ziv Gan-Or
,
Joshua Geiger
,
Anni Moore
,
Patrick May
,
Rejko Krüger
,
David Goldstein
,
Grisel Lopez
,
Nahid Tayebi
,
Ellen Sidransky
,
Anthony Sotis
,
Gauthaman Sukumar
,
Camille Alba
,
Nathaniel Lott
,
Elisa Mcgrath Martinez
,
Meila Tuck
,
Jatinder Singh
,
Dagmar Bacikova
,
Xijun Zhang
,
Daniel Hupalo
,
Adelani Adeleye
,
Matthew Wilkerson
,
Harvey Pollard
,
Lucy Norcliffe-Kaufmann
,
Jose-Alberto Palma
,
Horacio Kaufmann
,
Vikram Shakkottai
,
Matthew Perkins
,
Kathy Newell
,
Thomas Gasser
,
Claudia Schulte
,
Francesco Landi
,
Erika Salvi
,
Daniele Cusi
,
Eliezer Masliah
,
Ronald Kim
,
Chad Caraway
,
Edwin Monuki
,
Maura Brunetti
,
Ted Dawson
,
Liana Rosenthal
,
Marilyn Albert
,
Olga Pletnikova
,
Juan Troncoso
,
Margaret Flanagan
,
Qinwen Mao
,
Eileen Bigio
,
Eloy Rodríguez-Rodríguez
,
Jon Infante
,
Carmen Lage
,
Isabel González-Aramburu
,
Pascual Sanchez-Juan
,
Bernardino Ghetti
,
Julia Keith
,
Sandra Black
,
Mario Masellis
,
Ekaterina Rogaeva
,
Charles Duyckaerts
(1)
,
Alexis Brice
(1)
,
Suzanne Lesage
(1)
,
Georgia Xiromerisiou
,
Matthew Barrett
,
Bension Tilley
,
Steve Gentleman
,
Giancarlo Logroscino
,
Geidy Serrano
,
Thomas Beach
,
Ian Mckeith
,
Alan Thomas
,
Johannes Attems
,
Christopher Morris
,
Laura Palmer
,
Seth Love
,
Claire Troakes
,
Safa Al-Sarraj
,
Angela Hodges
,
Dag Aarsland
,
Gregory Klein
,
Scott Kaiser
,
Randy Woltjer
,
Pau Pastor
,
Lynn Bekris
,
James Leverenz
,
Lilah Besser
,
Amanda Kuzma
,
Alan Renton
,
Alison Goate
,
David Bennett
,
Clemens Scherzer
,
Huw Morris
,
Raffaele Ferrari
,
Diego Albani
,
Stuart Pickering-Brown
,
Kelley Faber
,
Walter Kukull
,
Estrella Morenas-Rodriguez
,
Alberto Lleó
,
Juan Fortea
,
Daniel Alcolea
,
Jordi Clarimon
,
Mike Nalls
,
Luigi Ferrucci
,
Susan Resnick
,
Toshiko Tanaka
,
Tatiana Foroud
,
Neill Graff-Radford
,
Zbigniew Wszolek
,
Tanis Ferman
,
Bradley Boeve
,
John Hardy
,
Eric Topol
,
Ali Torkamani
,
Andrew Singleton
,
Mina Ryten
,
Dennis Dickson
,
Adriano Chiò
,
Owen Ross
,
J. Raphael Gibbs
,
Clifton Dalgard
,
Bryan Traynor
,
Sonja Scholz
Ruth Chia
- Function : Author
Marya Sabir
- Function : Author
Sara Bandres-Ciga
- Function : Author
Sara Saez-Atienzar
- Function : Author
Regina Reynolds
- Function : Author
- PersonId : 1275775
- ORCID : 0000-0001-6470-7919
Emil Gustavsson
- Function : Author
- PersonId : 1275777
- ORCID : 0000-0003-0541-7537
Ronald Walton
- Function : Author
Sarah Ahmed
- Function : Author
Coralie Viollet
- Function : Author
Jinhui Ding
- Function : Author
Mary Makarious
- Function : Author
Monica Diez-Fairen
- Function : Author
- PersonId : 1164011
- ORCID : 0000-0003-1882-0309
Makayla Portley
- Function : Author
- PersonId : 1379296
- ORCID : 0000-0003-2866-9198
Zalak Shah
- Function : Author
Yevgeniya Abramzon
- Function : Author
Dena Hernandez
- Function : Author
Cornelis Blauwendraat
- Function : Author
- PersonId : 1275774
- ORCID : 0000-0001-9358-8111
David Stone
- Function : Author
John Eicher
- Function : Author
Laura Parkkinen
- Function : Author
- PersonId : 1379297
- ORCID : 0000-0002-3392-8564
Olaf Ansorge
- Function : Author
Lorraine Clark
- Function : Author
Lawrence Honig
- Function : Author
Karen Marder
- Function : Author
Afina Lemstra
- Function : Author
Peter St George-Hyslop
- Function : Author
- PersonId : 1327491
- ORCID : 0000-0003-0796-7209
Elisabet Londos
- Function : Author
Kevin Morgan
- Function : Author
- PersonId : 1305547
- ORCID : 0000-0002-8217-2396
Tammaryn Lashley
- Function : Author
Thomas Warner
- Function : Author
Zane Jaunmuktane
- Function : Author
Douglas Galasko
- Function : Author
Isabel Santana
- Function : Author
Pentti Tienari
- Function : Author
- PersonId : 1379298
- ORCID : 0000-0001-5686-2900
Liisa Myllykangas
- Function : Author
Minna Oinas
- Function : Author
- PersonId : 1379299
- ORCID : 0000-0002-6150-091X
Nigel Cairns
- Function : Author
- PersonId : 1379300
- ORCID : 0000-0001-9858-3344
John Morris
- Function : Author
Glenda Halliday
- Function : Author
- PersonId : 1339576
- ORCID : 0000-0003-0422-8398
Vivianna van Deerlin
- Function : Author
- PersonId : 1215607
- ORCID : 0000-0002-7400-9097
John Trojanowski
- Function : Author
- PersonId : 1296291
- ORCID : 0000-0002-9239-8794
Maurizio Grassano
- Function : Author
Andrea Calvo
- Function : Author
- PersonId : 1215591
- ORCID : 0000-0002-5122-7243
Gabriele Mora
- Function : Author
Antonio Canosa
- Function : Author
Gianluca Floris
- Function : Author
Ryan Bohannan
- Function : Author
Francesca Brett
- Function : Author
Ziv Gan-Or
- Function : Author
- PersonId : 791221
- ORCID : 0000-0003-0332-234X
Joshua Geiger
- Function : Author
Anni Moore
- Function : Author
Patrick May
- Function : Author
- PersonId : 764895
- ORCID : 0000-0001-8698-3770
Rejko Krüger
- Function : Author
David Goldstein
- Function : Author
Grisel Lopez
- Function : Author
Nahid Tayebi
- Function : Author
- PersonId : 1379301
- ORCID : 0000-0002-1007-4957
Ellen Sidransky
- Function : Author
Anthony Sotis
- Function : Author
Gauthaman Sukumar
- Function : Author
Camille Alba
- Function : Author
Nathaniel Lott
- Function : Author
Elisa Mcgrath Martinez
- Function : Author
Meila Tuck
- Function : Author
Jatinder Singh
- Function : Author
Dagmar Bacikova
- Function : Author
Xijun Zhang
- Function : Author
Daniel Hupalo
- Function : Author
Adelani Adeleye
- Function : Author
Matthew Wilkerson
- Function : Author
Harvey Pollard
- Function : Author
Lucy Norcliffe-Kaufmann
- Function : Author
Jose-Alberto Palma
- Function : Author
Horacio Kaufmann
- Function : Author
- PersonId : 1379302
- ORCID : 0000-0002-1851-9981
Vikram Shakkottai
- Function : Author
- PersonId : 1379303
- ORCID : 0000-0003-2742-6469
Matthew Perkins
- Function : Author
- PersonId : 1379304
- ORCID : 0000-0001-7715-0638
Kathy Newell
- Function : Author
Thomas Gasser
- Function : Author
Claudia Schulte
- Function : Author
Francesco Landi
- Function : Author
Erika Salvi
- Function : Author
Daniele Cusi
- Function : Author
- PersonId : 1379305
- ORCID : 0000-0002-1006-7597
Eliezer Masliah
- Function : Author
Ronald Kim
- Function : Author
Chad Caraway
- Function : Author
Edwin Monuki
- Function : Author
Maura Brunetti
- Function : Author
Ted Dawson
- Function : Author
Liana Rosenthal
- Function : Author
Marilyn Albert
- Function : Author
Olga Pletnikova
- Function : Author
Juan Troncoso
- Function : Author
Margaret Flanagan
- Function : Author
Qinwen Mao
- Function : Author
- PersonId : 1379306
- ORCID : 0000-0001-7876-2046
Eileen Bigio
- Function : Author
Eloy Rodríguez-Rodríguez
- Function : Author
- PersonId : 1305587
- ORCID : 0000-0001-7742-677X
Jon Infante
- Function : Author
Carmen Lage
- Function : Author
Isabel González-Aramburu
- Function : Author
Pascual Sanchez-Juan
- Function : Author
- PersonId : 1305555
- ORCID : 0000-0002-6081-8037
Bernardino Ghetti
- Function : Author
Julia Keith
- Function : Author
Sandra Black
- Function : Author
- PersonId : 1379307
- ORCID : 0000-0001-7093-8289
Mario Masellis
- Function : Author
Ekaterina Rogaeva
- Function : Author
Alexis Brice
- Function : Author
- PersonId : 1104774
- ORCID : 0000-0002-0941-3990
- IdRef : 050512935
Georgia Xiromerisiou
- Function : Author
Matthew Barrett
- Function : Author
Bension Tilley
- Function : Author
Steve Gentleman
- Function : Author
Giancarlo Logroscino
- Function : Author
Geidy Serrano
- Function : Author
Thomas Beach
- Function : Author
Ian Mckeith
- Function : Author
Alan Thomas
- Function : Author
Johannes Attems
- Function : Author
Christopher Morris
- Function : Author
Laura Palmer
- Function : Author
Seth Love
- Function : Author
Claire Troakes
- Function : Author
- PersonId : 1379308
- ORCID : 0000-0002-1790-7376
Safa Al-Sarraj
- Function : Author
Angela Hodges
- Function : Author
- PersonId : 1379309
- ORCID : 0000-0002-5565-6678
Dag Aarsland
- Function : Author
Gregory Klein
- Function : Author
Scott Kaiser
- Function : Author
Randy Woltjer
- Function : Author
Pau Pastor
- Function : Author
- PersonId : 1305551
- ORCID : 0000-0002-7493-8777
Lynn Bekris
- Function : Author
James Leverenz
- Function : Author
Lilah Besser
- Function : Author
Amanda Kuzma
- Function : Author
Alan Renton
- Function : Author
- PersonId : 1305808
- ORCID : 0000-0001-6702-8268
Alison Goate
- Function : Author
- PersonId : 761457
- ORCID : 0000-0002-0576-2472
- IdRef : 186309759
David Bennett
- Function : Author
Clemens Scherzer
- Function : Author
- PersonId : 1379310
- ORCID : 0000-0002-0567-9193
Huw Morris
- Function : Author
- PersonId : 1358679
- ORCID : 0000-0002-5473-3774
Raffaele Ferrari
- Function : Author
Diego Albani
- Function : Author
- PersonId : 785158
- ORCID : 0000-0002-7050-6723
Stuart Pickering-Brown
- Function : Author
- PersonId : 1305788
- ORCID : 0000-0003-1561-6054
Kelley Faber
- Function : Author
Walter Kukull
- Function : Author
Estrella Morenas-Rodriguez
- Function : Author
Alberto Lleó
- Function : Author
Juan Fortea
- Function : Author
Daniel Alcolea
- Function : Author
- PersonId : 797376
- ORCID : 0000-0002-3819-3245
Jordi Clarimon
- Function : Author
Mike Nalls
- Function : Author
Luigi Ferrucci
- Function : Author
- PersonId : 1277143
- ORCID : 0000-0002-6273-1613
Susan Resnick
- Function : Author
Toshiko Tanaka
- Function : Author
Tatiana Foroud
- Function : Author
- PersonId : 1359527
- ORCID : 0000-0002-5549-2212
Neill Graff-Radford
- Function : Author
Zbigniew Wszolek
- Function : Author
Tanis Ferman
- Function : Author
Bradley Boeve
- Function : Author
John Hardy
- Function : Author
Eric Topol
- Function : Author
- PersonId : 1379311
- ORCID : 0000-0002-1478-4729
Ali Torkamani
- Function : Author
Andrew Singleton
- Function : Author
Mina Ryten
- Function : Author
- PersonId : 1275783
- ORCID : 0000-0001-9520-6957
Dennis Dickson
- Function : Author
Adriano Chiò
- Function : Author
- PersonId : 764480
- ORCID : 0000-0001-9579-5341
Owen Ross
- Function : Author
- PersonId : 1339573
- ORCID : 0000-0003-4813-756X
J. Raphael Gibbs
- Function : Author
- PersonId : 1379312
- ORCID : 0000-0002-6985-0658
Clifton Dalgard
- Function : Author
Bryan Traynor
- Function : Author
Sonja Scholz
- Function : Author
- PersonId : 1275782
- ORCID : 0000-0002-6623-0429
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 disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.