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A meta-analysis of genome-wide association studies identifies multiple longevity genes
Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percenti...
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2019
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694136/ https://www.ncbi.nlm.nih.gov/pubmed/31413261 http://dx.doi.org/10.1038/s41467-019-11558-2 |
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| author | Deelen, Joris Evans, Daniel S. Arking, Dan E. Tesi, Niccolò Nygaard, Marianne Liu, Xiaomin Wojczynski, Mary K. Biggs, Mary L. van der Spek, Ashley Atzmon, Gil Ware, Erin B. Sarnowski, Chloé Smith, Albert V. Seppälä, Ilkka Cordell, Heather J. Dose, Janina Amin, Najaf Arnold, Alice M. Ayers, Kristin L. Barzilai, Nir Becker, Elizabeth J. Beekman, Marian Blanché, Hélène Christensen, Kaare Christiansen, Lene Collerton, Joanna C. Cubaynes, Sarah Cummings, Steven R. Davies, Karen Debrabant, Birgit Deleuze, Jean-François Duncan, Rachel Faul, Jessica D. Franceschi, Claudio Galan, Pilar Gudnason, Vilmundur Harris, Tamara B. Huisman, Martijn Hurme, Mikko A. Jagger, Carol Jansen, Iris Jylhä, Marja Kähönen, Mika Karasik, David Kardia, Sharon L. R. Kingston, Andrew Kirkwood, Thomas B. L. Launer, Lenore J. Lehtimäki, Terho Lieb, Wolfgang Lyytikäinen, Leo-Pekka Martin-Ruiz, Carmen Min, Junxia Nebel, Almut Newman, Anne B. Nie, Chao Nohr, Ellen A. Orwoll, Eric S. Perls, Thomas T. Province, Michael A. Psaty, Bruce M. Raitakari, Olli T. Reinders, Marcel J. T. Robine, Jean-Marie Rotter, Jerome I. Sebastiani, Paola Smith, Jennifer Sørensen, Thorkild I. A. Taylor, Kent D. Uitterlinden, André G. van der Flier, Wiesje van der Lee, Sven J. van Duijn, Cornelia M. van Heemst, Diana Vaupel, James W. Weir, David Ye, Kenny Zeng, Yi Zheng, Wanlin Holstege, Henne Kiel, Douglas P. Lunetta, Kathryn L. Slagboom, P. Eline Murabito, Joanne M. |
| author_facet | Deelen, Joris Evans, Daniel S. Arking, Dan E. Tesi, Niccolò Nygaard, Marianne Liu, Xiaomin Wojczynski, Mary K. Biggs, Mary L. van der Spek, Ashley Atzmon, Gil Ware, Erin B. Sarnowski, Chloé Smith, Albert V. Seppälä, Ilkka Cordell, Heather J. Dose, Janina Amin, Najaf Arnold, Alice M. Ayers, Kristin L. Barzilai, Nir Becker, Elizabeth J. Beekman, Marian Blanché, Hélène Christensen, Kaare Christiansen, Lene Collerton, Joanna C. Cubaynes, Sarah Cummings, Steven R. Davies, Karen Debrabant, Birgit Deleuze, Jean-François Duncan, Rachel Faul, Jessica D. Franceschi, Claudio Galan, Pilar Gudnason, Vilmundur Harris, Tamara B. Huisman, Martijn Hurme, Mikko A. Jagger, Carol Jansen, Iris Jylhä, Marja Kähönen, Mika Karasik, David Kardia, Sharon L. R. Kingston, Andrew Kirkwood, Thomas B. L. Launer, Lenore J. Lehtimäki, Terho Lieb, Wolfgang Lyytikäinen, Leo-Pekka Martin-Ruiz, Carmen Min, Junxia Nebel, Almut Newman, Anne B. Nie, Chao Nohr, Ellen A. Orwoll, Eric S. Perls, Thomas T. Province, Michael A. Psaty, Bruce M. Raitakari, Olli T. Reinders, Marcel J. T. Robine, Jean-Marie Rotter, Jerome I. Sebastiani, Paola Smith, Jennifer Sørensen, Thorkild I. A. Taylor, Kent D. Uitterlinden, André G. van der Flier, Wiesje van der Lee, Sven J. van Duijn, Cornelia M. van Heemst, Diana Vaupel, James W. Weir, David Ye, Kenny Zeng, Yi Zheng, Wanlin Holstege, Henne Kiel, Douglas P. Lunetta, Kathryn L. Slagboom, P. Eline Murabito, Joanne M. |
| author_sort | Deelen, Joris |
| collection | PubMed |
| description | Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity. |
| format | Online Article Text |
| id | pubmed-6694136 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-66941362019-08-19 A meta-analysis of genome-wide association studies identifies multiple longevity genes Deelen, Joris Evans, Daniel S. Arking, Dan E. Tesi, Niccolò Nygaard, Marianne Liu, Xiaomin Wojczynski, Mary K. Biggs, Mary L. van der Spek, Ashley Atzmon, Gil Ware, Erin B. Sarnowski, Chloé Smith, Albert V. Seppälä, Ilkka Cordell, Heather J. Dose, Janina Amin, Najaf Arnold, Alice M. Ayers, Kristin L. Barzilai, Nir Becker, Elizabeth J. Beekman, Marian Blanché, Hélène Christensen, Kaare Christiansen, Lene Collerton, Joanna C. Cubaynes, Sarah Cummings, Steven R. Davies, Karen Debrabant, Birgit Deleuze, Jean-François Duncan, Rachel Faul, Jessica D. Franceschi, Claudio Galan, Pilar Gudnason, Vilmundur Harris, Tamara B. Huisman, Martijn Hurme, Mikko A. Jagger, Carol Jansen, Iris Jylhä, Marja Kähönen, Mika Karasik, David Kardia, Sharon L. R. Kingston, Andrew Kirkwood, Thomas B. L. Launer, Lenore J. Lehtimäki, Terho Lieb, Wolfgang Lyytikäinen, Leo-Pekka Martin-Ruiz, Carmen Min, Junxia Nebel, Almut Newman, Anne B. Nie, Chao Nohr, Ellen A. Orwoll, Eric S. Perls, Thomas T. Province, Michael A. Psaty, Bruce M. Raitakari, Olli T. Reinders, Marcel J. T. Robine, Jean-Marie Rotter, Jerome I. Sebastiani, Paola Smith, Jennifer Sørensen, Thorkild I. A. Taylor, Kent D. Uitterlinden, André G. van der Flier, Wiesje van der Lee, Sven J. van Duijn, Cornelia M. van Heemst, Diana Vaupel, James W. Weir, David Ye, Kenny Zeng, Yi Zheng, Wanlin Holstege, Henne Kiel, Douglas P. Lunetta, Kathryn L. Slagboom, P. Eline Murabito, Joanne M. Nat Commun Article Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity. Nature Publishing Group UK 2019-08-14 /pmc/articles/PMC6694136/ /pubmed/31413261 http://dx.doi.org/10.1038/s41467-019-11558-2 Text en © The Author(s) 2019 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/. |
| spellingShingle | Article Deelen, Joris Evans, Daniel S. Arking, Dan E. Tesi, Niccolò Nygaard, Marianne Liu, Xiaomin Wojczynski, Mary K. Biggs, Mary L. van der Spek, Ashley Atzmon, Gil Ware, Erin B. Sarnowski, Chloé Smith, Albert V. Seppälä, Ilkka Cordell, Heather J. Dose, Janina Amin, Najaf Arnold, Alice M. Ayers, Kristin L. Barzilai, Nir Becker, Elizabeth J. Beekman, Marian Blanché, Hélène Christensen, Kaare Christiansen, Lene Collerton, Joanna C. Cubaynes, Sarah Cummings, Steven R. Davies, Karen Debrabant, Birgit Deleuze, Jean-François Duncan, Rachel Faul, Jessica D. Franceschi, Claudio Galan, Pilar Gudnason, Vilmundur Harris, Tamara B. Huisman, Martijn Hurme, Mikko A. Jagger, Carol Jansen, Iris Jylhä, Marja Kähönen, Mika Karasik, David Kardia, Sharon L. R. Kingston, Andrew Kirkwood, Thomas B. L. Launer, Lenore J. Lehtimäki, Terho Lieb, Wolfgang Lyytikäinen, Leo-Pekka Martin-Ruiz, Carmen Min, Junxia Nebel, Almut Newman, Anne B. Nie, Chao Nohr, Ellen A. Orwoll, Eric S. Perls, Thomas T. Province, Michael A. Psaty, Bruce M. Raitakari, Olli T. Reinders, Marcel J. T. Robine, Jean-Marie Rotter, Jerome I. Sebastiani, Paola Smith, Jennifer Sørensen, Thorkild I. A. Taylor, Kent D. Uitterlinden, André G. van der Flier, Wiesje van der Lee, Sven J. van Duijn, Cornelia M. van Heemst, Diana Vaupel, James W. Weir, David Ye, Kenny Zeng, Yi Zheng, Wanlin Holstege, Henne Kiel, Douglas P. Lunetta, Kathryn L. Slagboom, P. Eline Murabito, Joanne M. A meta-analysis of genome-wide association studies identifies multiple longevity genes |
| title | A meta-analysis of genome-wide association studies identifies multiple longevity genes |
| title_full | A meta-analysis of genome-wide association studies identifies multiple longevity genes |
| title_fullStr | A meta-analysis of genome-wide association studies identifies multiple longevity genes |
| title_full_unstemmed | A meta-analysis of genome-wide association studies identifies multiple longevity genes |
| title_short | A meta-analysis of genome-wide association studies identifies multiple longevity genes |
| title_sort | meta-analysis of genome-wide association studies identifies multiple longevity genes |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694136/ https://www.ncbi.nlm.nih.gov/pubmed/31413261 http://dx.doi.org/10.1038/s41467-019-11558-2 |
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