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Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use
Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable(2,3) and etiologically related(4,5) behaviors that have been resistant to gene discovery efforts(6–11). In sample sizes up to 1.2 million individuals, we discovere...
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2019
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358542/ https://www.ncbi.nlm.nih.gov/pubmed/30643251 http://dx.doi.org/10.1038/s41588-018-0307-5 |
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| author | Liu, Mengzhen Jiang, Yu Wedow, Robbee Li, Yue Brazel, David M. Chen, Fang Datta, Gargi Davila-Velderrain, Jose McGuire, Daniel Tian, Chao Zhan, Xiaowei Choquet, Hélène Docherty, Anna R. Faul, Jessica D. Foerster, Johanna R. Fritsche, Lars G. Gabrielsen, Maiken Elvestad Gordon, Scott D. Haessler, Jeffrey Hottenga, Jouke-Jan Huang, Hongyan Jang, Seon-Kyeong Jansen, Philip R. Ling, Yueh Mägi, Reedik Matoba, Nana McMahon, George Mulas, Antonella Orrù, Valeria Palviainen, Teemu Pandit, Anita Reginsson, Gunnar W. Skogholt, Anne Heidi Smith, Jennifer A. Taylor, Amy E. Turman, Constance Willemsen, Gonneke Young, Hannah Young, Kendra A. Zajac, Gregory J. M. Zhao, Wei Zhou, Wei Bjornsdottir, Gyda Boardman, Jason D. Boehnke, Michael Boomsma, Dorret I. Chen, Chu Cucca, Francesco Davies, Gareth E. Eaton, Charles B. Ehringer, Marissa A. Esko, Tõnu Fiorillo, Edoardo Gillespie, Nathan A. Gudbjartsson, Daniel F. Haller, Toomas Harris, Kathleen Mullan Heath, Andrew C. Hewitt, John K. Hickie, Ian B. Hokanson, John E. Hopfer, Christian J. Hunter, David J. Iacono, William G. Johnson, Eric O. Kamatani, Yoichiro Kardia, Sharon L. R. Keller, Matthew C. Kellis, Manolis Kooperberg, Charles Kraft, Peter Krauter, Kenneth S. Laakso, Markku Lind, Penelope A. Loukola, Anu Lutz, Sharon M. Madden, Pamela A. F. Martin, Nicholas G. McGue, Matt McQueen, Matthew B. Medland, Sarah E. Metspalu, Andres Mohlke, Karen L. Nielsen, Jonas B. Okada, Yukinori Peters, Ulrike Polderman, Tinca J. C. Posthuma, Danielle Reiner, Alexander P. Rice, John P. Rimm, Eric Rose, Richard J. Runarsdottir, Valgerdur Stallings, Michael C. Stančáková, Alena Stefansson, Hreinn Thai, Khanh K. Tindle, Hilary A. Tyrfingsson, Thorarinn Wall, Tamara L. Weir, David R. Weisner, Constance Whitfield, John B. Winsvold, Bendik Slagsvold Yin, Jie Zuccolo, Luisa Bierut, Laura J. Hveem, Kristian Lee, James J. Munafo, Marcus R. Saccone, Nancy L. Willer, Cristen J. Cornelis, Marilyn C. David, Sean P. Hinds, David Jorgenson, Eric Kaprio, Jaakko Stitzel, Jerry A. Stefansson, Kari Thorgeirsson, Thorgeir E. Abecasis, Goncalo Liu, Dajiang J. Vrieze, Scott |
| author_facet | Liu, Mengzhen Jiang, Yu Wedow, Robbee Li, Yue Brazel, David M. Chen, Fang Datta, Gargi Davila-Velderrain, Jose McGuire, Daniel Tian, Chao Zhan, Xiaowei Choquet, Hélène Docherty, Anna R. Faul, Jessica D. Foerster, Johanna R. Fritsche, Lars G. Gabrielsen, Maiken Elvestad Gordon, Scott D. Haessler, Jeffrey Hottenga, Jouke-Jan Huang, Hongyan Jang, Seon-Kyeong Jansen, Philip R. Ling, Yueh Mägi, Reedik Matoba, Nana McMahon, George Mulas, Antonella Orrù, Valeria Palviainen, Teemu Pandit, Anita Reginsson, Gunnar W. Skogholt, Anne Heidi Smith, Jennifer A. Taylor, Amy E. Turman, Constance Willemsen, Gonneke Young, Hannah Young, Kendra A. Zajac, Gregory J. M. Zhao, Wei Zhou, Wei Bjornsdottir, Gyda Boardman, Jason D. Boehnke, Michael Boomsma, Dorret I. Chen, Chu Cucca, Francesco Davies, Gareth E. Eaton, Charles B. Ehringer, Marissa A. Esko, Tõnu Fiorillo, Edoardo Gillespie, Nathan A. Gudbjartsson, Daniel F. Haller, Toomas Harris, Kathleen Mullan Heath, Andrew C. Hewitt, John K. Hickie, Ian B. Hokanson, John E. Hopfer, Christian J. Hunter, David J. Iacono, William G. Johnson, Eric O. Kamatani, Yoichiro Kardia, Sharon L. R. Keller, Matthew C. Kellis, Manolis Kooperberg, Charles Kraft, Peter Krauter, Kenneth S. Laakso, Markku Lind, Penelope A. Loukola, Anu Lutz, Sharon M. Madden, Pamela A. F. Martin, Nicholas G. McGue, Matt McQueen, Matthew B. Medland, Sarah E. Metspalu, Andres Mohlke, Karen L. Nielsen, Jonas B. Okada, Yukinori Peters, Ulrike Polderman, Tinca J. C. Posthuma, Danielle Reiner, Alexander P. Rice, John P. Rimm, Eric Rose, Richard J. Runarsdottir, Valgerdur Stallings, Michael C. Stančáková, Alena Stefansson, Hreinn Thai, Khanh K. Tindle, Hilary A. Tyrfingsson, Thorarinn Wall, Tamara L. Weir, David R. Weisner, Constance Whitfield, John B. Winsvold, Bendik Slagsvold Yin, Jie Zuccolo, Luisa Bierut, Laura J. Hveem, Kristian Lee, James J. Munafo, Marcus R. Saccone, Nancy L. Willer, Cristen J. Cornelis, Marilyn C. David, Sean P. Hinds, David Jorgenson, Eric Kaprio, Jaakko Stitzel, Jerry A. Stefansson, Kari Thorgeirsson, Thorgeir E. Abecasis, Goncalo Liu, Dajiang J. Vrieze, Scott |
| author_sort | Liu, Mengzhen |
| collection | PubMed |
| description | Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable(2,3) and etiologically related(4,5) behaviors that have been resistant to gene discovery efforts(6–11). In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures. |
| format | Online Article Text |
| id | pubmed-6358542 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-63585422019-07-14 Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use Liu, Mengzhen Jiang, Yu Wedow, Robbee Li, Yue Brazel, David M. Chen, Fang Datta, Gargi Davila-Velderrain, Jose McGuire, Daniel Tian, Chao Zhan, Xiaowei Choquet, Hélène Docherty, Anna R. Faul, Jessica D. Foerster, Johanna R. Fritsche, Lars G. Gabrielsen, Maiken Elvestad Gordon, Scott D. Haessler, Jeffrey Hottenga, Jouke-Jan Huang, Hongyan Jang, Seon-Kyeong Jansen, Philip R. Ling, Yueh Mägi, Reedik Matoba, Nana McMahon, George Mulas, Antonella Orrù, Valeria Palviainen, Teemu Pandit, Anita Reginsson, Gunnar W. Skogholt, Anne Heidi Smith, Jennifer A. Taylor, Amy E. Turman, Constance Willemsen, Gonneke Young, Hannah Young, Kendra A. Zajac, Gregory J. M. Zhao, Wei Zhou, Wei Bjornsdottir, Gyda Boardman, Jason D. Boehnke, Michael Boomsma, Dorret I. Chen, Chu Cucca, Francesco Davies, Gareth E. Eaton, Charles B. Ehringer, Marissa A. Esko, Tõnu Fiorillo, Edoardo Gillespie, Nathan A. Gudbjartsson, Daniel F. Haller, Toomas Harris, Kathleen Mullan Heath, Andrew C. Hewitt, John K. Hickie, Ian B. Hokanson, John E. Hopfer, Christian J. Hunter, David J. Iacono, William G. Johnson, Eric O. Kamatani, Yoichiro Kardia, Sharon L. R. Keller, Matthew C. Kellis, Manolis Kooperberg, Charles Kraft, Peter Krauter, Kenneth S. Laakso, Markku Lind, Penelope A. Loukola, Anu Lutz, Sharon M. Madden, Pamela A. F. Martin, Nicholas G. McGue, Matt McQueen, Matthew B. Medland, Sarah E. Metspalu, Andres Mohlke, Karen L. Nielsen, Jonas B. Okada, Yukinori Peters, Ulrike Polderman, Tinca J. C. Posthuma, Danielle Reiner, Alexander P. Rice, John P. Rimm, Eric Rose, Richard J. Runarsdottir, Valgerdur Stallings, Michael C. Stančáková, Alena Stefansson, Hreinn Thai, Khanh K. Tindle, Hilary A. Tyrfingsson, Thorarinn Wall, Tamara L. Weir, David R. Weisner, Constance Whitfield, John B. Winsvold, Bendik Slagsvold Yin, Jie Zuccolo, Luisa Bierut, Laura J. Hveem, Kristian Lee, James J. Munafo, Marcus R. Saccone, Nancy L. Willer, Cristen J. Cornelis, Marilyn C. David, Sean P. Hinds, David Jorgenson, Eric Kaprio, Jaakko Stitzel, Jerry A. Stefansson, Kari Thorgeirsson, Thorgeir E. Abecasis, Goncalo Liu, Dajiang J. Vrieze, Scott Nat Genet Article Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable(2,3) and etiologically related(4,5) behaviors that have been resistant to gene discovery efforts(6–11). In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures. 2019-01-14 2019-02 /pmc/articles/PMC6358542/ /pubmed/30643251 http://dx.doi.org/10.1038/s41588-018-0307-5 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 Liu, Mengzhen Jiang, Yu Wedow, Robbee Li, Yue Brazel, David M. Chen, Fang Datta, Gargi Davila-Velderrain, Jose McGuire, Daniel Tian, Chao Zhan, Xiaowei Choquet, Hélène Docherty, Anna R. Faul, Jessica D. Foerster, Johanna R. Fritsche, Lars G. Gabrielsen, Maiken Elvestad Gordon, Scott D. Haessler, Jeffrey Hottenga, Jouke-Jan Huang, Hongyan Jang, Seon-Kyeong Jansen, Philip R. Ling, Yueh Mägi, Reedik Matoba, Nana McMahon, George Mulas, Antonella Orrù, Valeria Palviainen, Teemu Pandit, Anita Reginsson, Gunnar W. Skogholt, Anne Heidi Smith, Jennifer A. Taylor, Amy E. Turman, Constance Willemsen, Gonneke Young, Hannah Young, Kendra A. Zajac, Gregory J. M. Zhao, Wei Zhou, Wei Bjornsdottir, Gyda Boardman, Jason D. Boehnke, Michael Boomsma, Dorret I. Chen, Chu Cucca, Francesco Davies, Gareth E. Eaton, Charles B. Ehringer, Marissa A. Esko, Tõnu Fiorillo, Edoardo Gillespie, Nathan A. Gudbjartsson, Daniel F. Haller, Toomas Harris, Kathleen Mullan Heath, Andrew C. Hewitt, John K. Hickie, Ian B. Hokanson, John E. Hopfer, Christian J. Hunter, David J. Iacono, William G. Johnson, Eric O. Kamatani, Yoichiro Kardia, Sharon L. R. Keller, Matthew C. Kellis, Manolis Kooperberg, Charles Kraft, Peter Krauter, Kenneth S. Laakso, Markku Lind, Penelope A. Loukola, Anu Lutz, Sharon M. Madden, Pamela A. F. Martin, Nicholas G. McGue, Matt McQueen, Matthew B. Medland, Sarah E. Metspalu, Andres Mohlke, Karen L. Nielsen, Jonas B. Okada, Yukinori Peters, Ulrike Polderman, Tinca J. C. Posthuma, Danielle Reiner, Alexander P. Rice, John P. Rimm, Eric Rose, Richard J. Runarsdottir, Valgerdur Stallings, Michael C. Stančáková, Alena Stefansson, Hreinn Thai, Khanh K. Tindle, Hilary A. Tyrfingsson, Thorarinn Wall, Tamara L. Weir, David R. Weisner, Constance Whitfield, John B. Winsvold, Bendik Slagsvold Yin, Jie Zuccolo, Luisa Bierut, Laura J. Hveem, Kristian Lee, James J. Munafo, Marcus R. Saccone, Nancy L. Willer, Cristen J. Cornelis, Marilyn C. David, Sean P. Hinds, David Jorgenson, Eric Kaprio, Jaakko Stitzel, Jerry A. Stefansson, Kari Thorgeirsson, Thorgeir E. Abecasis, Goncalo Liu, Dajiang J. Vrieze, Scott Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use |
| title | Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use |
| title_full | Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use |
| title_fullStr | Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use |
| title_full_unstemmed | Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use |
| title_short | Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use |
| title_sort | association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358542/ https://www.ncbi.nlm.nih.gov/pubmed/30643251 http://dx.doi.org/10.1038/s41588-018-0307-5 |
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