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

Ruth Chia; Laura Palmer; Seth Love; Sonja Scholz; 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, Laura Palmer, Seth Love, Sonja Scholz^*, American Genome Center

^*Corresponding author for this work

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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
Early online date	15 Feb 2021
DOIs	https://doi.org/10.1038/s41588-021-00785-3
Publication status	Published - Mar 2021

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Cerebrovascular and Dementia Research Group

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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's disease and Parkinson'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 Laura Palmer and Seth Love and Sonja Scholz and \{American Genome Center\}",

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

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AU - Sabir, Marya S

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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 - Palmer, Laura

AU - Love, Seth

AU - Scholz, Sonja

AU - American Genome Center

PY - 2021/3

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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.

U2 - 10.1038/s41588-021-00785-3

DO - 10.1038/s41588-021-00785-3

M3 - Article (Academic Journal)

C2 - 33589841

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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