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Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure
We conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood prot...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2023
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333277/ https://www.ncbi.nlm.nih.gov/pubmed/37429843 http://dx.doi.org/10.1038/s41467-023-39253-3 |
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| author | Rasooly, Danielle Peloso, Gina M. Pereira, Alexandre C. Dashti, Hesam Giambartolomei, Claudia Wheeler, Eleanor Aung, Nay Ferolito, Brian R. Pietzner, Maik Farber-Eger, Eric H. Wells, Quinn Stanton Kosik, Nicole M. Gaziano, Liam Posner, Daniel C. Bento, A. Patrícia Hui, Qin Liu, Chang Aragam, Krishna Wang, Zeyuan Charest, Brian Huffman, Jennifer E. Wilson, Peter W. F. Phillips, Lawrence S. Whittaker, John Munroe, Patricia B. Petersen, Steffen E. Cho, Kelly Leach, Andrew R. Magariños, María Paula Gaziano, John Michael Langenberg, Claudia Sun, Yan V. Joseph, Jacob Casas, Juan P. |
| author_facet | Rasooly, Danielle Peloso, Gina M. Pereira, Alexandre C. Dashti, Hesam Giambartolomei, Claudia Wheeler, Eleanor Aung, Nay Ferolito, Brian R. Pietzner, Maik Farber-Eger, Eric H. Wells, Quinn Stanton Kosik, Nicole M. Gaziano, Liam Posner, Daniel C. Bento, A. Patrícia Hui, Qin Liu, Chang Aragam, Krishna Wang, Zeyuan Charest, Brian Huffman, Jennifer E. Wilson, Peter W. F. Phillips, Lawrence S. Whittaker, John Munroe, Patricia B. Petersen, Steffen E. Cho, Kelly Leach, Andrew R. Magariños, María Paula Gaziano, John Michael Langenberg, Claudia Sun, Yan V. Joseph, Jacob Casas, Juan P. |
| author_sort | Rasooly, Danielle |
| collection | PubMed |
| description | We conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven (CAMK2D, PRKD1, PRKD3, MAPK3, TNFSF12, APOC3 and NAE1) proteins as potential targets for interventions to be used in primary prevention of heart failure. |
| format | Online Article Text |
| id | pubmed-10333277 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-103332772023-07-12 Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure Rasooly, Danielle Peloso, Gina M. Pereira, Alexandre C. Dashti, Hesam Giambartolomei, Claudia Wheeler, Eleanor Aung, Nay Ferolito, Brian R. Pietzner, Maik Farber-Eger, Eric H. Wells, Quinn Stanton Kosik, Nicole M. Gaziano, Liam Posner, Daniel C. Bento, A. Patrícia Hui, Qin Liu, Chang Aragam, Krishna Wang, Zeyuan Charest, Brian Huffman, Jennifer E. Wilson, Peter W. F. Phillips, Lawrence S. Whittaker, John Munroe, Patricia B. Petersen, Steffen E. Cho, Kelly Leach, Andrew R. Magariños, María Paula Gaziano, John Michael Langenberg, Claudia Sun, Yan V. Joseph, Jacob Casas, Juan P. Nat Commun Article We conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven (CAMK2D, PRKD1, PRKD3, MAPK3, TNFSF12, APOC3 and NAE1) proteins as potential targets for interventions to be used in primary prevention of heart failure. Nature Publishing Group UK 2023-07-10 /pmc/articles/PMC10333277/ /pubmed/37429843 http://dx.doi.org/10.1038/s41467-023-39253-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Rasooly, Danielle Peloso, Gina M. Pereira, Alexandre C. Dashti, Hesam Giambartolomei, Claudia Wheeler, Eleanor Aung, Nay Ferolito, Brian R. Pietzner, Maik Farber-Eger, Eric H. Wells, Quinn Stanton Kosik, Nicole M. Gaziano, Liam Posner, Daniel C. Bento, A. Patrícia Hui, Qin Liu, Chang Aragam, Krishna Wang, Zeyuan Charest, Brian Huffman, Jennifer E. Wilson, Peter W. F. Phillips, Lawrence S. Whittaker, John Munroe, Patricia B. Petersen, Steffen E. Cho, Kelly Leach, Andrew R. Magariños, María Paula Gaziano, John Michael Langenberg, Claudia Sun, Yan V. Joseph, Jacob Casas, Juan P. Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure |
| title | Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure |
| title_full | Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure |
| title_fullStr | Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure |
| title_full_unstemmed | Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure |
| title_short | Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure |
| title_sort | genome-wide association analysis and mendelian randomization proteomics identify drug targets for heart failure |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333277/ https://www.ncbi.nlm.nih.gov/pubmed/37429843 http://dx.doi.org/10.1038/s41467-023-39253-3 |
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