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; Rejko Krüger; The American Genome Center

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, Rejko Krüger, The American Genome Center

Transversal Translational Medicine

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

237 Citations (Scopus)

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 - Mar 2021

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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., ... The American Genome Center (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{c0e15871689440f689c15e20c1682e00,

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 Rejko Kr{\"u}ger and {The American Genome Center}",

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.",

year = "2021",

month = mar,

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

language = "English",

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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, Krüger, R & The American Genome Center 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 - Krüger, Rejko

AU - The American Genome Center

PY - 2021/3

Y1 - 2021/3

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.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/33589841

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DO - 10.1038/s41588-021-00785-3

M3 - Article

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AN - SCOPUS:85101937262

SN - 1061-4036

VL - 53

SP - 294

EP - 303

JO - Nature Genetics

JF - Nature Genetics

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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