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Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
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 com...
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2021
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946812/ https://www.ncbi.nlm.nih.gov/pubmed/33589841 http://dx.doi.org/10.1038/s41588-021-00785-3 |
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| author | Chia, Ruth Sabir, Marya S. Bandres-Ciga, Sara Saez-Atienzar, Sara Reynolds, Regina H. Gustavsson, Emil Walton, Ronald L. Ahmed, Sarah Viollet, Coralie Ding, Jinhui Makarious, Mary B. Diez-Fairen, Monica Portley, Makayla K. Shah, Zalak Abramzon, Yevgeniya Hernandez, Dena G. Blauwendraat, Cornelis Stone, David J. Eicher, John Parkkinen, Laura Ansorge, Olaf Clark, Lorraine Honig, Lawrence S. Marder, Karen Lemstra, Afina St George-Hyslop, Peter Londos, Elisabet Morgan, Kevin Lashley, Tammaryn Warner, Thomas T. Jaunmuktane, Zane Galasko, Douglas Santana, Isabel Tienari, Pentti J. Myllykangas, Liisa Oinas, Minna Cairns, Nigel J. Morris, John C. Halliday, Glenda M. Van Deerlin, Vivianna M. Trojanowski, John Q. Grassano, Maurizio Calvo, Andrea Mora, Gabriele Canosa, Antonio Floris, Gianluca Bohannan, Ryan C. Brett, Francesca Gan-Or, Ziv Geiger, Joshua T. Moore, Anni May, Patrick Krüger, Rejko Goldstein, David S. Lopez, Grisel Tayebi, Nahid Sidransky, Ellen Norcliffe-Kaufmann, Lucy Palma, Jose-Alberto Kaufmann, Horacio Shakkottai, Vikram G. Perkins, Matthew Newell, Kathy L. Gasser, Thomas Schulte, Claudia Landi, Francesco Salvi, Erika Cusi, Daniele Masliah, Eliezer Kim, Ronald C. Caraway, Chad A. Monuki, Edwin S. Brunetti, Maura Dawson, Ted M. Rosenthal, Liana S. Albert, Marilyn S. Pletnikova, Olga Troncoso, Juan C. Flanagan, Margaret E. Mao, Qinwen Bigio, Eileen H. Rodríguez-Rodríguez, Eloy Infante, Jon Lage, Carmen González-Aramburu, Isabel Sanchez-Juan, Pascual Ghetti, Bernardino Keith, Julia Black, Sandra E. Masellis, Mario Rogaeva, Ekaterina Duyckaerts, Charles Brice, Alexis Lesage, Suzanne Xiromerisiou, Georgia Barrett, Matthew J. Tilley, Bension S. Gentleman, Steve Logroscino, Giancarlo Serrano, Geidy E. Beach, Thomas G. McKeith, Ian G. Thomas, Alan J. Attems, Johannes Morris, Christopher M. Palmer, Laura Love, Seth Troakes, Claire Al-Sarraj, Safa Hodges, Angela K. Aarsland, Dag Klein, Gregory Kaiser, Scott M. Woltjer, Randy Pastor, Pau Bekris, Lynn M. Leverenz, James B. Besser, Lilah M. Kuzma, Amanda Renton, Alan E. Goate, Alison Bennett, David A. Scherzer, Clemens R. Morris, Huw R. Ferrari, Raffaele Albani, Diego Pickering-Brown, Stuart Faber, Kelley Kukull, Walter A. Morenas-Rodriguez, Estrella Lleó, Alberto Fortea, Juan Alcolea, Daniel Clarimon, Jordi Nalls, Mike A. Ferrucci, Luigi Resnick, Susan M. Tanaka, Toshiko Foroud, Tatiana M. Graff-Radford, Neill R. Wszolek, Zbigniew K. Ferman, Tanis Boeve, Bradley F. Hardy, John A. Topol, Eric J. Torkamani, Ali Singleton, Andrew B. Ryten, Mina Dickson, Dennis W. Chiò, Adriano Ross, Owen A. Gibbs, J. Raphael Dalgard, Clifton L. Traynor, Bryan J. Scholz, Sonja W. |
| author_facet | Chia, Ruth Sabir, Marya S. Bandres-Ciga, Sara Saez-Atienzar, Sara Reynolds, Regina H. Gustavsson, Emil Walton, Ronald L. Ahmed, Sarah Viollet, Coralie Ding, Jinhui Makarious, Mary B. Diez-Fairen, Monica Portley, Makayla K. Shah, Zalak Abramzon, Yevgeniya Hernandez, Dena G. Blauwendraat, Cornelis Stone, David J. Eicher, John Parkkinen, Laura Ansorge, Olaf Clark, Lorraine Honig, Lawrence S. Marder, Karen Lemstra, Afina St George-Hyslop, Peter Londos, Elisabet Morgan, Kevin Lashley, Tammaryn Warner, Thomas T. Jaunmuktane, Zane Galasko, Douglas Santana, Isabel Tienari, Pentti J. Myllykangas, Liisa Oinas, Minna Cairns, Nigel J. Morris, John C. Halliday, Glenda M. Van Deerlin, Vivianna M. Trojanowski, John Q. Grassano, Maurizio Calvo, Andrea Mora, Gabriele Canosa, Antonio Floris, Gianluca Bohannan, Ryan C. Brett, Francesca Gan-Or, Ziv Geiger, Joshua T. Moore, Anni May, Patrick Krüger, Rejko Goldstein, David S. Lopez, Grisel Tayebi, Nahid Sidransky, Ellen Norcliffe-Kaufmann, Lucy Palma, Jose-Alberto Kaufmann, Horacio Shakkottai, Vikram G. Perkins, Matthew Newell, Kathy L. Gasser, Thomas Schulte, Claudia Landi, Francesco Salvi, Erika Cusi, Daniele Masliah, Eliezer Kim, Ronald C. Caraway, Chad A. Monuki, Edwin S. Brunetti, Maura Dawson, Ted M. Rosenthal, Liana S. Albert, Marilyn S. Pletnikova, Olga Troncoso, Juan C. Flanagan, Margaret E. Mao, Qinwen Bigio, Eileen H. Rodríguez-Rodríguez, Eloy Infante, Jon Lage, Carmen González-Aramburu, Isabel Sanchez-Juan, Pascual Ghetti, Bernardino Keith, Julia Black, Sandra E. Masellis, Mario Rogaeva, Ekaterina Duyckaerts, Charles Brice, Alexis Lesage, Suzanne Xiromerisiou, Georgia Barrett, Matthew J. Tilley, Bension S. Gentleman, Steve Logroscino, Giancarlo Serrano, Geidy E. Beach, Thomas G. McKeith, Ian G. Thomas, Alan J. Attems, Johannes Morris, Christopher M. Palmer, Laura Love, Seth Troakes, Claire Al-Sarraj, Safa Hodges, Angela K. Aarsland, Dag Klein, Gregory Kaiser, Scott M. Woltjer, Randy Pastor, Pau Bekris, Lynn M. Leverenz, James B. Besser, Lilah M. Kuzma, Amanda Renton, Alan E. Goate, Alison Bennett, David A. Scherzer, Clemens R. Morris, Huw R. Ferrari, Raffaele Albani, Diego Pickering-Brown, Stuart Faber, Kelley Kukull, Walter A. Morenas-Rodriguez, Estrella Lleó, Alberto Fortea, Juan Alcolea, Daniel Clarimon, Jordi Nalls, Mike A. Ferrucci, Luigi Resnick, Susan M. Tanaka, Toshiko Foroud, Tatiana M. Graff-Radford, Neill R. Wszolek, Zbigniew K. Ferman, Tanis Boeve, Bradley F. Hardy, John A. Topol, Eric J. Torkamani, Ali Singleton, Andrew B. Ryten, Mina Dickson, Dennis W. Chiò, Adriano Ross, Owen A. Gibbs, J. Raphael Dalgard, Clifton L. Traynor, Bryan J. Scholz, Sonja W. |
| author_sort | Chia, Ruth |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-7946812 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-79468122021-08-15 Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture Chia, Ruth Sabir, Marya S. Bandres-Ciga, Sara Saez-Atienzar, Sara Reynolds, Regina H. Gustavsson, Emil Walton, Ronald L. Ahmed, Sarah Viollet, Coralie Ding, Jinhui Makarious, Mary B. Diez-Fairen, Monica Portley, Makayla K. Shah, Zalak Abramzon, Yevgeniya Hernandez, Dena G. Blauwendraat, Cornelis Stone, David J. Eicher, John Parkkinen, Laura Ansorge, Olaf Clark, Lorraine Honig, Lawrence S. Marder, Karen Lemstra, Afina St George-Hyslop, Peter Londos, Elisabet Morgan, Kevin Lashley, Tammaryn Warner, Thomas T. Jaunmuktane, Zane Galasko, Douglas Santana, Isabel Tienari, Pentti J. Myllykangas, Liisa Oinas, Minna Cairns, Nigel J. Morris, John C. Halliday, Glenda M. Van Deerlin, Vivianna M. Trojanowski, John Q. Grassano, Maurizio Calvo, Andrea Mora, Gabriele Canosa, Antonio Floris, Gianluca Bohannan, Ryan C. Brett, Francesca Gan-Or, Ziv Geiger, Joshua T. Moore, Anni May, Patrick Krüger, Rejko Goldstein, David S. Lopez, Grisel Tayebi, Nahid Sidransky, Ellen Norcliffe-Kaufmann, Lucy Palma, Jose-Alberto Kaufmann, Horacio Shakkottai, Vikram G. Perkins, Matthew Newell, Kathy L. Gasser, Thomas Schulte, Claudia Landi, Francesco Salvi, Erika Cusi, Daniele Masliah, Eliezer Kim, Ronald C. Caraway, Chad A. Monuki, Edwin S. Brunetti, Maura Dawson, Ted M. Rosenthal, Liana S. Albert, Marilyn S. Pletnikova, Olga Troncoso, Juan C. Flanagan, Margaret E. Mao, Qinwen Bigio, Eileen H. Rodríguez-Rodríguez, Eloy Infante, Jon Lage, Carmen González-Aramburu, Isabel Sanchez-Juan, Pascual Ghetti, Bernardino Keith, Julia Black, Sandra E. Masellis, Mario Rogaeva, Ekaterina Duyckaerts, Charles Brice, Alexis Lesage, Suzanne Xiromerisiou, Georgia Barrett, Matthew J. Tilley, Bension S. Gentleman, Steve Logroscino, Giancarlo Serrano, Geidy E. Beach, Thomas G. McKeith, Ian G. Thomas, Alan J. Attems, Johannes Morris, Christopher M. Palmer, Laura Love, Seth Troakes, Claire Al-Sarraj, Safa Hodges, Angela K. Aarsland, Dag Klein, Gregory Kaiser, Scott M. Woltjer, Randy Pastor, Pau Bekris, Lynn M. Leverenz, James B. Besser, Lilah M. Kuzma, Amanda Renton, Alan E. Goate, Alison Bennett, David A. Scherzer, Clemens R. Morris, Huw R. Ferrari, Raffaele Albani, Diego Pickering-Brown, Stuart Faber, Kelley Kukull, Walter A. Morenas-Rodriguez, Estrella Lleó, Alberto Fortea, Juan Alcolea, Daniel Clarimon, Jordi Nalls, Mike A. Ferrucci, Luigi Resnick, Susan M. Tanaka, Toshiko Foroud, Tatiana M. Graff-Radford, Neill R. Wszolek, Zbigniew K. Ferman, Tanis Boeve, Bradley F. Hardy, John A. Topol, Eric J. Torkamani, Ali Singleton, Andrew B. Ryten, Mina Dickson, Dennis W. Chiò, Adriano Ross, Owen A. Gibbs, J. Raphael Dalgard, Clifton L. Traynor, Bryan J. Scholz, Sonja W. Nat Genet Article 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. 2021-02-15 2021-03 /pmc/articles/PMC7946812/ /pubmed/33589841 http://dx.doi.org/10.1038/s41588-021-00785-3 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Chia, Ruth Sabir, Marya S. Bandres-Ciga, Sara Saez-Atienzar, Sara Reynolds, Regina H. Gustavsson, Emil Walton, Ronald L. Ahmed, Sarah Viollet, Coralie Ding, Jinhui Makarious, Mary B. Diez-Fairen, Monica Portley, Makayla K. Shah, Zalak Abramzon, Yevgeniya Hernandez, Dena G. Blauwendraat, Cornelis Stone, David J. Eicher, John Parkkinen, Laura Ansorge, Olaf Clark, Lorraine Honig, Lawrence S. Marder, Karen Lemstra, Afina St George-Hyslop, Peter Londos, Elisabet Morgan, Kevin Lashley, Tammaryn Warner, Thomas T. Jaunmuktane, Zane Galasko, Douglas Santana, Isabel Tienari, Pentti J. Myllykangas, Liisa Oinas, Minna Cairns, Nigel J. Morris, John C. Halliday, Glenda M. Van Deerlin, Vivianna M. Trojanowski, John Q. Grassano, Maurizio Calvo, Andrea Mora, Gabriele Canosa, Antonio Floris, Gianluca Bohannan, Ryan C. Brett, Francesca Gan-Or, Ziv Geiger, Joshua T. Moore, Anni May, Patrick Krüger, Rejko Goldstein, David S. Lopez, Grisel Tayebi, Nahid Sidransky, Ellen Norcliffe-Kaufmann, Lucy Palma, Jose-Alberto Kaufmann, Horacio Shakkottai, Vikram G. Perkins, Matthew Newell, Kathy L. Gasser, Thomas Schulte, Claudia Landi, Francesco Salvi, Erika Cusi, Daniele Masliah, Eliezer Kim, Ronald C. Caraway, Chad A. Monuki, Edwin S. Brunetti, Maura Dawson, Ted M. Rosenthal, Liana S. Albert, Marilyn S. Pletnikova, Olga Troncoso, Juan C. Flanagan, Margaret E. Mao, Qinwen Bigio, Eileen H. Rodríguez-Rodríguez, Eloy Infante, Jon Lage, Carmen González-Aramburu, Isabel Sanchez-Juan, Pascual Ghetti, Bernardino Keith, Julia Black, Sandra E. Masellis, Mario Rogaeva, Ekaterina Duyckaerts, Charles Brice, Alexis Lesage, Suzanne Xiromerisiou, Georgia Barrett, Matthew J. Tilley, Bension S. Gentleman, Steve Logroscino, Giancarlo Serrano, Geidy E. Beach, Thomas G. McKeith, Ian G. Thomas, Alan J. Attems, Johannes Morris, Christopher M. Palmer, Laura Love, Seth Troakes, Claire Al-Sarraj, Safa Hodges, Angela K. Aarsland, Dag Klein, Gregory Kaiser, Scott M. Woltjer, Randy Pastor, Pau Bekris, Lynn M. Leverenz, James B. Besser, Lilah M. Kuzma, Amanda Renton, Alan E. Goate, Alison Bennett, David A. Scherzer, Clemens R. Morris, Huw R. Ferrari, Raffaele Albani, Diego Pickering-Brown, Stuart Faber, Kelley Kukull, Walter A. Morenas-Rodriguez, Estrella Lleó, Alberto Fortea, Juan Alcolea, Daniel Clarimon, Jordi Nalls, Mike A. Ferrucci, Luigi Resnick, Susan M. Tanaka, Toshiko Foroud, Tatiana M. Graff-Radford, Neill R. Wszolek, Zbigniew K. Ferman, Tanis Boeve, Bradley F. Hardy, John A. Topol, Eric J. Torkamani, Ali Singleton, Andrew B. Ryten, Mina Dickson, Dennis W. Chiò, Adriano Ross, Owen A. Gibbs, J. Raphael Dalgard, Clifton L. Traynor, Bryan J. Scholz, Sonja W. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture |
| title | Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture |
| title_full | Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture |
| title_fullStr | Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture |
| title_full_unstemmed | Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture |
| title_short | Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture |
| title_sort | genome sequencing analysis identifies new loci associated with lewy body dementia and provides insights into its genetic architecture |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946812/ https://www.ncbi.nlm.nih.gov/pubmed/33589841 http://dx.doi.org/10.1038/s41588-021-00785-3 |
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