Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

Ruth Chia; Marya S. Sabir; Sara Bandres-Ciga; Sara Saez-Atienzar; Regina H. Reynolds; Emil Gustavsson; Ronald L. Walton; Sarah Ahmed; Coralie Viollet; Jinhui Ding; Mary B. Makarious; Monica Diez-Fairen; Makayla K. Portley; Zalak Shah; Yevgeniya Abramzon; Dena G. Hernandez; Cornelis Blauwendraat; David J. Stone; John Eicher; Laura Parkkinen; Olaf Ansorge; Lorraine Clark; Lawrence S. Honig; Karen Marder; Afina Lemstra; Peter St George-Hyslop; Elisabet Londos; Kevin Morgan; Tammaryn Lashley; Thomas T. Warner; Zane Jaunmuktane; Douglas Galasko; Isabel Santana; Pentti J. Tienari; Liisa Myllykangas; Minna Oinas; Nigel J. Cairns; John C. Morris; Glenda M. Halliday; Vivianna M. van Deerlin; John Q. Trojanowski; Maurizio Grassano; Andrea Calvo; Gabriele Mora; Antonio Canosa; Gianluca Floris; Ryan C. Bohannan; Francesca Brett; Ziv Gan-Or; Joshua T. Geiger; Anni Moore; Patrick May; Rejko Krüger; David S. Goldstein; Grisel Lopez; Nahid Tayebi; Ellen Sidransky; The American Genome Center; Anthony R. Sotis; Gauthaman Sukumar; Camille Alba; Nathaniel Lott; Elisa McGrath Martinez; Meila Tuck; Jatinder Singh; Dagmar Bacikova; Xijun Zhang; Daniel N. Hupalo; Adelani Adeleye; Matthew D. Wilkerson; Harvey B. Pollard; Lucy Norcliffe-Kaufmann; Jose-Alberto Palma; Horacio Kaufmann; Vikram G. Shakkottai; Matthew Perkins; Kathy L. Newell; Thomas Gasser; Claudia Schulte; Francesco Landi; Erika Salvi; Daniele Cusi; Eliezer Masliah; Ronald C. Kim; Chad A. Caraway; Edwin S. Monuki; Maura Brunetti; Ted M. Dawson; Liana S. Rosenthal; Marilyn S. Albert; Olga Pletnikova; Juan C. Troncoso; Margaret E. Flanagan; Qinwen Mao; Eileen H. Bigio; Eloy Rodríguez-Rodríguez; Jon Infante; Carmen Lage; Isabel González-Aramburu; Pascual Sanchez-Juan; Bernardino Ghetti; Julia Keith; Sandra E. Black; Mario Masellis; Ekaterina Rogaeva; Charles Duyckaerts; Alexis Brice; Suzanne Lesage; Georgia Xiromerisiou; Matthew J. Barrett; Bension S. Tilley; Steve Gentleman; Giancarlo Logroscino; Geidy E. Serrano; Thomas G. Beach; Ian G. McKeith; Alan J. Thomas; Johannes Attems; Christopher M. Morris; Laura Palmer; Seth Love; Claire Troakes; Safa Al-Sarraj; Angela K. Hodges; Dag Aarsland; Gregory Klein; Scott M. Kaiser; Randy Woltjer; Pau Pastor; Lynn M. Bekris; James B. Leverenz; Lilah M. Besser; Amanda Kuzma; Alan E. Renton; Alison Goate; David A. Bennett; Clemens R. Scherzer; Huw R. Morris; Raffaele Ferrari; Diego Albani; Stuart Pickering-Brown; Kelley Faber; Walter A. Kukull; Estrella Morenas-Rodriguez; Alberto Lleó; Juan Fortea; Daniel Alcolea; Jordi Clarimon; Mike A. Nalls; Luigi Ferrucci; Susan M. Resnick; Toshiko Tanaka; Tatiana M. Foroud; Neill R. Graff-Radford; Zbigniew K. Wszolek; Tanis Ferman; Bradley F. Boeve; John A. Hardy; Eric J. Topol; Ali Torkamani; Andrew B. Singleton; Mina Ryten; Dennis W. Dickson; Adriano Chiò; Owen A. Ross; J. Raphael Gibbs; Clifton L. Dalgard; Bryan J. Traynor; Sonja W. Scholz

doi:10.1038/s41588-021-00785-3

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

Ruth Chia, Marya S. Sabir, Sara Bandres-Ciga, Sara Saez-Atienzar, Regina H. Reynolds, Emil Gustavsson, Ronald L. Walton, Sarah Ahmed, Coralie Viollet, Jinhui Ding, Mary B. Makarious, Monica Diez-Fairen, Makayla K. Portley, Zalak Shah, Yevgeniya Abramzon, Dena G. Hernandez, Cornelis Blauwendraat, David J. Stone, John Eicher, Laura ParkkinenOlaf Ansorge, Lorraine Clark, Lawrence S. Honig, Karen Marder, Afina Lemstra, Peter St George-Hyslop, Elisabet Londos, Kevin Morgan, Tammaryn Lashley, Thomas T. Warner, Zane Jaunmuktane, Douglas Galasko, Isabel Santana, Pentti J. Tienari, Liisa Myllykangas, Minna Oinas, Nigel J. Cairns, John C. Morris, Glenda M. Halliday, Vivianna M. van Deerlin, John Q. Trojanowski, Maurizio Grassano, Andrea Calvo, Gabriele Mora, Antonio Canosa, Gianluca Floris, Ryan C. Bohannan, Francesca Brett, Ziv Gan-Or, Joshua T. Geiger, Anni Moore, Patrick May, Rejko Krüger, David S. Goldstein, Grisel Lopez, Nahid Tayebi, Ellen Sidransky, The American Genome Center, Anthony R. Sotis, Gauthaman Sukumar, Camille Alba, Nathaniel Lott, Elisa McGrath Martinez, Meila Tuck, Jatinder Singh, Dagmar Bacikova, Xijun Zhang, Daniel N. Hupalo, Adelani Adeleye, Matthew D. Wilkerson, Harvey B. Pollard, Lucy Norcliffe-Kaufmann, Jose-Alberto Palma, Horacio Kaufmann, Vikram G. Shakkottai, Matthew Perkins, Kathy L. Newell, Thomas Gasser, Claudia Schulte, Francesco Landi, Erika Salvi, Daniele Cusi, Eliezer Masliah, Ronald C. Kim, Chad A. Caraway, Edwin S. Monuki, Maura Brunetti, Ted M. Dawson, Liana S. Rosenthal, Marilyn S. Albert, Olga Pletnikova, Juan C. Troncoso, Margaret E. Flanagan, Qinwen Mao, Eileen H. Bigio, Eloy Rodríguez-Rodríguez, Jon Infante, Carmen Lage, Isabel González-Aramburu, Pascual Sanchez-Juan, Bernardino Ghetti, Julia Keith, Sandra E. Black, Mario Masellis, Ekaterina Rogaeva, Charles Duyckaerts, Alexis Brice, Suzanne Lesage, Georgia Xiromerisiou, Matthew J. Barrett, Bension S. Tilley, Steve Gentleman, Giancarlo Logroscino, Geidy E. Serrano, Thomas G. Beach, Ian G. McKeith, Alan J. Thomas, Johannes Attems, Christopher M. Morris, Laura Palmer, Seth Love, Claire Troakes, Safa Al-Sarraj, Angela K. Hodges, Dag Aarsland, Gregory Klein, Scott M. Kaiser, Randy Woltjer, Pau Pastor, Lynn M. Bekris, James B. Leverenz, Lilah M. Besser, Amanda Kuzma, Alan E. Renton, Alison Goate, David A. Bennett, Clemens R. Scherzer, Huw R. Morris, Raffaele Ferrari, Diego Albani, Stuart Pickering-Brown, Kelley Faber, Walter A. Kukull, Estrella Morenas-Rodriguez, Alberto Lleó, Juan Fortea, Daniel Alcolea, Jordi Clarimon, Mike A. Nalls, Luigi Ferrucci, Susan M. Resnick, Toshiko Tanaka, Tatiana M. Foroud, Neill R. Graff-Radford, Zbigniew K. Wszolek, Tanis Ferman, Bradley F. Boeve, John A. Hardy, Eric J. Topol, Ali Torkamani, Andrew B. Singleton, Mina Ryten, Dennis W. Dickson, Adriano Chiò, Owen A. Ross, J. Raphael Gibbs, Clifton L. Dalgard, Bryan J. Traynor, Sonja W. Scholz^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	294-303
Number of pages	10
Journal	Nature Genetics
Volume	53
Issue number	3
DOIs	https://doi.org/10.1038/s41588-021-00785-3
Publication status	Published - 1 Mar 2021

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10.1038/s41588-021-00785-3

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Chia, R., Sabir, M. S., Bandres-Ciga, S., Saez-Atienzar, S., Reynolds, R. H., Gustavsson, E., Walton, R. L., Ahmed, S., Viollet, C., Ding, J., Makarious, M. B., Diez-Fairen, M., Portley, M. K., Shah, Z., Abramzon, Y., Hernandez, D. G., Blauwendraat, C., Stone, D. J., Eicher, J., ... Scholz, S. W. (2021). Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture. Nature Genetics, 53(3), 294-303. https://doi.org/10.1038/s41588-021-00785-3

@article{5be66236d71d4cb4983cfc5a899086ef,

title = "Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture",

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{\textquoteright}s disease and Parkinson{\textquoteright}s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.",

author = "Ruth Chia and Sabir, {Marya S.} and Sara Bandres-Ciga and Sara Saez-Atienzar and Reynolds, {Regina H.} and Emil Gustavsson and Walton, {Ronald L.} and Sarah Ahmed and Coralie Viollet and Jinhui Ding and Makarious, {Mary B.} and Monica Diez-Fairen and Portley, {Makayla K.} and Zalak Shah and Yevgeniya Abramzon and Hernandez, {Dena G.} and Cornelis Blauwendraat and Stone, {David J.} and John Eicher and Laura Parkkinen and Olaf Ansorge and Lorraine Clark and Honig, {Lawrence S.} and Karen Marder and Afina Lemstra and {St George-Hyslop}, Peter and Elisabet Londos and Kevin Morgan and Tammaryn Lashley and Warner, {Thomas T.} and Zane Jaunmuktane and Douglas Galasko and Isabel Santana and Tienari, {Pentti J.} and Liisa Myllykangas and Minna Oinas and Cairns, {Nigel J.} and Morris, {John C.} and Halliday, {Glenda M.} and {van Deerlin}, {Vivianna M.} and Trojanowski, {John Q.} and Maurizio Grassano and Andrea Calvo and Gabriele Mora and Antonio Canosa and Gianluca Floris and Bohannan, {Ryan C.} and Francesca Brett and Ziv Gan-Or and Geiger, {Joshua T.} and Anni Moore and Patrick May and Rejko Kr{\"u}ger and Goldstein, {David S.} and Grisel Lopez and Nahid Tayebi and Ellen Sidransky and {The American Genome Center} and Sotis, {Anthony R.} and Gauthaman Sukumar and Camille Alba and Nathaniel Lott and Martinez, {Elisa McGrath} and Meila Tuck and Jatinder Singh and Dagmar Bacikova and Xijun Zhang and Hupalo, {Daniel N.} and Adelani Adeleye and Wilkerson, {Matthew D.} and Pollard, {Harvey B.} and Lucy Norcliffe-Kaufmann and Jose-Alberto Palma and Horacio Kaufmann and Shakkottai, {Vikram G.} and Matthew Perkins and Newell, {Kathy L.} and Thomas Gasser and Claudia Schulte and Francesco Landi and Erika Salvi and Daniele Cusi and Eliezer Masliah and Kim, {Ronald C.} and Caraway, {Chad A.} and Monuki, {Edwin S.} and Maura Brunetti and Dawson, {Ted M.} and Rosenthal, {Liana S.} and Albert, {Marilyn S.} and Olga Pletnikova and Troncoso, {Juan C.} and Flanagan, {Margaret E.} and Qinwen Mao and Bigio, {Eileen H.} and Eloy Rodr{\'i}guez-Rodr{\'i}guez and Jon Infante and Carmen Lage and Isabel Gonz{\'a}lez-Aramburu and Pascual Sanchez-Juan and Bernardino Ghetti and Julia Keith and Black, {Sandra E.} and Mario Masellis and Ekaterina Rogaeva and Charles Duyckaerts and Alexis Brice and Suzanne Lesage and Georgia Xiromerisiou and Barrett, {Matthew J.} and Tilley, {Bension S.} and Steve Gentleman and Giancarlo Logroscino and Serrano, {Geidy E.} and Beach, {Thomas G.} and McKeith, {Ian G.} and Thomas, {Alan J.} and Johannes Attems and Morris, {Christopher M.} and Laura Palmer and Seth Love and Claire Troakes and Safa Al-Sarraj and Hodges, {Angela K.} and Dag Aarsland and Gregory Klein and Kaiser, {Scott M.} and Randy Woltjer and Pau Pastor and Bekris, {Lynn M.} and Leverenz, {James B.} and Besser, {Lilah M.} and Amanda Kuzma and Renton, {Alan E.} and Alison Goate and Bennett, {David A.} and Scherzer, {Clemens R.} and Morris, {Huw R.} and Raffaele Ferrari and Diego Albani and Stuart Pickering-Brown and Kelley Faber and Kukull, {Walter A.} and Estrella Morenas-Rodriguez and Alberto Lle{\'o} and Juan Fortea and Daniel Alcolea and Jordi Clarimon and Nalls, {Mike A.} and Luigi Ferrucci and Resnick, {Susan M.} and Toshiko Tanaka and Foroud, {Tatiana M.} and Graff-Radford, {Neill R.} and Wszolek, {Zbigniew K.} and Tanis Ferman and Boeve, {Bradley F.} and Hardy, {John A.} and Topol, {Eric J.} and Ali Torkamani and Singleton, {Andrew B.} and Mina Ryten and Dickson, {Dennis W.} and Adriano Chi{\`o} and Ross, {Owen A.} and Gibbs, {J. Raphael} and Dalgard, {Clifton L.} and Traynor, {Bryan J.} and Scholz, {Sonja W.}",

note = "Publisher Copyright: {\textcopyright} 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = mar,

day = "1",

doi = "10.1038/s41588-021-00785-3",

language = "English",

volume = "53",

pages = "294--303",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "3",

}

Chia, R, Sabir, MS, Bandres-Ciga, S, Saez-Atienzar, S, Reynolds, RH, Gustavsson, E, Walton, RL, Ahmed, S, Viollet, C, Ding, J, Makarious, MB, Diez-Fairen, M, Portley, MK, Shah, Z, Abramzon, Y, Hernandez, DG, Blauwendraat, C, Stone, DJ, Eicher, J, Parkkinen, L, Ansorge, O, Clark, L, Honig, LS, Marder, K, Lemstra, A, St George-Hyslop, P, Londos, E, Morgan, K, Lashley, T, Warner, TT, Jaunmuktane, Z, Galasko, D, Santana, I, Tienari, PJ, Myllykangas, L, Oinas, M, Cairns, NJ, Morris, JC, Halliday, GM, van Deerlin, VM, Trojanowski, JQ, Grassano, M, Calvo, A, Mora, G, Canosa, A, Floris, G, Bohannan, RC, Brett, F, Gan-Or, Z, Geiger, JT, Moore, A, May, P, Krüger, R, Goldstein, DS, Lopez, G, Tayebi, N, Sidransky, E, The American Genome Center, Sotis, AR, Sukumar, G, Alba, C, Lott, N, Martinez, EM, Tuck, M, Singh, J, Bacikova, D, Zhang, X, Hupalo, DN, Adeleye, A, Wilkerson, MD, Pollard, HB, Norcliffe-Kaufmann, L, Palma, J-A, Kaufmann, H, Shakkottai, VG, Perkins, M, Newell, KL, Gasser, T, Schulte, C, Landi, F, Salvi, E, Cusi, D, Masliah, E, Kim, RC, Caraway, CA, Monuki, ES, Brunetti, M, Dawson, TM, Rosenthal, LS, Albert, MS, Pletnikova, O, Troncoso, JC, Flanagan, ME, Mao, Q, Bigio, EH, Rodríguez-Rodríguez, E, Infante, J, Lage, C, González-Aramburu, I, Sanchez-Juan, P, Ghetti, B, Keith, J, Black, SE, Masellis, M, Rogaeva, E, Duyckaerts, C, Brice, A, Lesage, S, Xiromerisiou, G, Barrett, MJ, Tilley, BS, Gentleman, S, Logroscino, G, Serrano, GE, Beach, TG, McKeith, IG, Thomas, AJ, Attems, J, Morris, CM, Palmer, L, Love, S, Troakes, C, Al-Sarraj, S, Hodges, AK, Aarsland, D, Klein, G, Kaiser, SM, Woltjer, R, Pastor, P, Bekris, LM, Leverenz, JB, Besser, LM, Kuzma, A, Renton, AE, Goate, A, Bennett, DA, Scherzer, CR, Morris, HR, Ferrari, R, Albani, D, Pickering-Brown, S, Faber, K, Kukull, WA, Morenas-Rodriguez, E, Lleó, A, Fortea, J, Alcolea, D, Clarimon, J, Nalls, MA, Ferrucci, L, Resnick, SM, Tanaka, T, Foroud, TM, Graff-Radford, NR, Wszolek, ZK, Ferman, T, Boeve, BF, Hardy, JA, Topol, EJ, Torkamani, A, Singleton, AB, Ryten, M, Dickson, DW, Chiò, A, Ross, OA, Gibbs, JR, Dalgard, CL, Traynor, BJ & Scholz, SW 2021, 'Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture', Nature Genetics, vol. 53, no. 3, pp. 294-303. https://doi.org/10.1038/s41588-021-00785-3

TY - JOUR

T1 - Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

AU - Chia, Ruth

AU - Sabir, Marya S.

AU - Bandres-Ciga, Sara

AU - Saez-Atienzar, Sara

AU - Reynolds, Regina H.

AU - Gustavsson, Emil

AU - Walton, Ronald L.

AU - Ahmed, Sarah

AU - Viollet, Coralie

AU - Ding, Jinhui

AU - Makarious, Mary B.

AU - Diez-Fairen, Monica

AU - Portley, Makayla K.

AU - Shah, Zalak

AU - Abramzon, Yevgeniya

AU - Hernandez, Dena G.

AU - Blauwendraat, Cornelis

AU - Stone, David J.

AU - Eicher, John

AU - Parkkinen, Laura

AU - Ansorge, Olaf

AU - Clark, Lorraine

AU - Honig, Lawrence S.

AU - Marder, Karen

AU - Lemstra, Afina

AU - St George-Hyslop, Peter

AU - Londos, Elisabet

AU - Morgan, Kevin

AU - Lashley, Tammaryn

AU - Warner, Thomas T.

AU - Jaunmuktane, Zane

AU - Galasko, Douglas

AU - Santana, Isabel

AU - Tienari, Pentti J.

AU - Myllykangas, Liisa

AU - Oinas, Minna

AU - Cairns, Nigel J.

AU - Morris, John C.

AU - Halliday, Glenda M.

AU - van Deerlin, Vivianna M.

AU - Trojanowski, John Q.

AU - Grassano, Maurizio

AU - Calvo, Andrea

AU - Mora, Gabriele

AU - Canosa, Antonio

AU - Floris, Gianluca

AU - Bohannan, Ryan C.

AU - Brett, Francesca

AU - Gan-Or, Ziv

AU - Geiger, Joshua T.

AU - Moore, Anni

AU - May, Patrick

AU - Krüger, Rejko

AU - Goldstein, David S.

AU - Lopez, Grisel

AU - Tayebi, Nahid

AU - Sidransky, Ellen

AU - The American Genome Center

AU - Sotis, Anthony R.

AU - Sukumar, Gauthaman

AU - Alba, Camille

AU - Lott, Nathaniel

AU - Martinez, Elisa McGrath

AU - Tuck, Meila

AU - Singh, Jatinder

AU - Bacikova, Dagmar

AU - Zhang, Xijun

AU - Hupalo, Daniel N.

AU - Adeleye, Adelani

AU - Wilkerson, Matthew D.

AU - Pollard, Harvey B.

AU - Norcliffe-Kaufmann, Lucy

AU - Palma, Jose-Alberto

AU - Kaufmann, Horacio

AU - Shakkottai, Vikram G.

AU - Perkins, Matthew

AU - Newell, Kathy L.

AU - Gasser, Thomas

AU - Schulte, Claudia

AU - Landi, Francesco

AU - Salvi, Erika

AU - Cusi, Daniele

AU - Masliah, Eliezer

AU - Kim, Ronald C.

AU - Caraway, Chad A.

AU - Monuki, Edwin S.

AU - Brunetti, Maura

AU - Dawson, Ted M.

AU - Rosenthal, Liana S.

AU - Albert, Marilyn S.

AU - Pletnikova, Olga

AU - Troncoso, Juan C.

AU - Flanagan, Margaret E.

AU - Mao, Qinwen

AU - Bigio, Eileen H.

AU - Rodríguez-Rodríguez, Eloy

AU - Infante, Jon

AU - Lage, Carmen

AU - González-Aramburu, Isabel

AU - Sanchez-Juan, Pascual

AU - Ghetti, Bernardino

AU - Keith, Julia

AU - Black, Sandra E.

AU - Masellis, Mario

AU - Rogaeva, Ekaterina

AU - Duyckaerts, Charles

AU - Brice, Alexis

AU - Lesage, Suzanne

AU - Xiromerisiou, Georgia

AU - Barrett, Matthew J.

AU - Tilley, Bension S.

AU - Gentleman, Steve

AU - Logroscino, Giancarlo

AU - Serrano, Geidy E.

AU - Beach, Thomas G.

AU - McKeith, Ian G.

AU - Thomas, Alan J.

AU - Attems, Johannes

AU - Morris, Christopher M.

AU - Palmer, Laura

AU - Love, Seth

AU - Troakes, Claire

AU - Al-Sarraj, Safa

AU - Hodges, Angela K.

AU - Aarsland, Dag

AU - Klein, Gregory

AU - Kaiser, Scott M.

AU - Woltjer, Randy

AU - Pastor, Pau

AU - Bekris, Lynn M.

AU - Leverenz, James B.

AU - Besser, Lilah M.

AU - Kuzma, Amanda

AU - Renton, Alan E.

AU - Goate, Alison

AU - Bennett, David A.

AU - Scherzer, Clemens R.

AU - Morris, Huw R.

AU - Ferrari, Raffaele

AU - Albani, Diego

AU - Pickering-Brown, Stuart

AU - Faber, Kelley

AU - Kukull, Walter A.

AU - Morenas-Rodriguez, Estrella

AU - Lleó, Alberto

AU - Fortea, Juan

AU - Alcolea, Daniel

AU - Clarimon, Jordi

AU - Nalls, Mike A.

AU - Ferrucci, Luigi

AU - Resnick, Susan M.

AU - Tanaka, Toshiko

AU - Foroud, Tatiana M.

AU - Graff-Radford, Neill R.

AU - Wszolek, Zbigniew K.

AU - Ferman, Tanis

AU - Boeve, Bradley F.

AU - Hardy, John A.

AU - Topol, Eric J.

AU - Torkamani, Ali

AU - Singleton, Andrew B.

AU - Ryten, Mina

AU - Dickson, Dennis W.

AU - Chiò, Adriano

AU - Ross, Owen A.

AU - Gibbs, J. Raphael

AU - Dalgard, Clifton L.

AU - Traynor, Bryan J.

AU - Scholz, Sonja W.

N1 - Publisher Copyright: © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/3/1

Y1 - 2021/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85101937262&partnerID=8YFLogxK

U2 - 10.1038/s41588-021-00785-3

DO - 10.1038/s41588-021-00785-3

M3 - Article

C2 - 33589841

VL - 53

SP - 294

EP - 303

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

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