Skip to search
Skip to main content
Back to Search
Start Over
A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure
Authors :
Sung, Yun J. Winkler, Thomas W. de las Fuentes, Lisa Bentley, Amy R. Brown, Michael R. Kraja, Aldi T. Schwander, Karen Ntalla, Ioanna Guo, Xiuqing Franceschini, Nora Lu, Yingchang Cheng, Ching-Yu Sim, Xueling Vojinovic, Dina Marten, Jonathan Musani, Solomon K. Li, Changwei Feitosa, Mary F. Kilpelainen, Tuomas O. Richard, Melissa A. Noordam, Raymond Aslibekyan, Stella Aschard, Hugues Bartz, Traci M. Dorajoo, Rajkumar Liu, Yongmei Manning, Alisa K. Rankinen, Tuomo Smith, Albert Vernon Tajuddin, Salman M. Tayo, Bamidele O. Warren, Helen R. Zhao, Wei Zhou, Yanhua Matoba, Nana Sofer, Tamar Alver, Maris Amini, Marzyeh Boissel, Mathilde Chai, Jin Fang Chen, Xu Divers, Jasmin Gandin, Ilaria Gao, Chuan Giulianini, Franco Goel, Anuj Harris, Sarah E. Hartwig, Fernando Pires Horimoto, Andrea R. V. R. Hsu, Fang-Chi Jackson, Anne U. Kahonen, Mika Kasturiratne, Anuradhani Kuhnel, Brigitte Leander, Karin Lee, Wen-Jane Lin, Keng-Hung Luan, Jian' an McKenzie, Colin A. Meian, He Nelson, Christopher P. Rauramaa, Rainer Schupf, Nicole Scott, Robert A. Sheu, Wayne H. H. Stancakova, Alena Takeuchi, Fumihiko van der Most, Peter J. Varga, Tibor V. Wang, Heming Wang, Yajuan Ware, Erin B. Weiss, Stefan Wen, Wanqing Yanek, Lisa R. Zhang, Weihua Zhao, Jing Hua Afaq, Saima Alfred, Tamuno Amin, Najaf Arking, Dan Aung, Tin Barr, R. Graham Bielak, Lawrence F. Boerwinkle, Eric Bottinger, Erwin P. Braund, Peter S. Brody, Jennifer A. Broeckel, Ulrich Cabrera, Claudia P. Cade, Brian Caizheng, Yu Campbell, Archie Canouil, Mickael Chakravarti, Aravinda Chauhan, Ganesh Christensen, Kaare Cocca, Massimiliano Collins, Francis S. Connell, John M. de Mutsert, Renee de Silva, H. Janaka Debette, Stephanie Dorr, Marcus Duan, Qing Eaton, Charles B. Ehret, Georg Evangelou, Evangelos Faul, Jessica D. Fisher, Virginia A. Forouhi, Nita G. Franco, Oscar H. Friedlander, Yechiel Gao, He Gigante, Bruna Graff, Misa Gu, C. Charles Gu, Dongfeng Gupta, Preeti Hagenaars, Saskia P. Harris, Tamara B. He, Jiang Heikkinen, Sami Heng, Chew-Kiat Hirata, Makoto Hofman, Albert Howard, Barbara V. Hunt, Steven Irvin, Marguerite R. Jia, Yucheng Joehanes, Roby Justice, Anne E. Katsuya, Tomohiro Kaufman, Joel Kerrison, Nicola D. Khor, Chiea Chuen Koh, Woon-Puay Koistinen, Heikki A. Komulainen, Pirjo Kooperberg, Charles Krieger, Jose E. Kubo, Michiaki Kuusisto, Johanna Langefeld, Carl D. Langenberg, Claudia Launer, Lenore J. Lehne, Benjamin Lewis, Cora E. Li, Yize Lim, Sing Hui Lin, Shiow Liu, Ching-Ti Liu, Jianjun Liu, Jingmin Liu, Kiang Liu, Yeheng Loh, Marie Lohman, Kurt K. Long, Jirong Louie, Tin Magi, Reedik Mahajan, Anubha Meitinger, Thomas Metspalu, Andres Milani, Lili Momozawa, Yukihide Morris, Andrew P. Mosley, Thomas H., Jr. Munson, Peter Murray, Alison D. Nalls, Mike A. Nasri, Ubaydah Norris, Jill M. North, Kari Ogunniyi, Adesola Padmanabhan, Sandosh Palmas, Walter R. Palmer, Nicholette D. Pankow, James S. Pedersen, Nancy L. Peters, Annette Peyser, Patricia A. Polasek, Ozren Raitakari, Olli T. Renström, Frida Rice, Treva K. Ridker, Paul M. Robino, Antonietta Robinson, Jennifer G. Rose, Lynda M. Rudan, Igor Sabanayagam, Charumathi Salako, Babatunde L. Sandow, Kevin Schmidt, Carsten O. Schreiner, Pamela J. Scott, William R. Seshadri, Sudha Sever, Peter Sitlani, Colleen M. Smith, Jennifer A. Snieder, Harold Starr, John M. Strauch, Konstantin Tang, Hua Taylor, Kent D. Teo, Yik Ying Tham, Yih Chung Ultterlinden, Andre G. Waldenberger, Melanie Wang, Lihua Wang, Ya X. Bin Wei, Wen Williams, Christine Wilson, Gregory Wojczynski, Mary K. Yao, Jie Yuan, Jian-Min Zonderman, Alan B. Becker, Diane M. Boehnke, Michael Bowden, Donald W. Chambers, John C. Chen, Yii-Der Ida de Faire, Ulf Deary, Ian J. Esko, Tonu Farrall, Martin Forrester, Terrence Franks, Paul W. Freedman, Barry I. Froguel, Philippe Gasparini, Paolo Gieger, Christian Horta, Bernardo Lessa Hung, Yi-Jen Jonas, Jost B. Kato, Norihiro Kooner, Jaspal S. Laakso, Markku Lehtimaki, Terho Liang, Kae-Woei Magnusson, Patrik K. E. Newman, Anne B. Oldehinkel, Albertine J. Pereira, Alexandre C. Redline, Susan Rettig, Rainer Samani, Nilesh J. Scott, James Shu, Xiao-Ou van der Harst, Pim Wagenknecht, Lynne E. Wareham, Nicholas J. Watkins, Hugh Weir, David R. Wickremasinghe, Ananda R. Wu, Tangchun Zheng, Wei Kamatani, Yoichiro Laurie, Cathy C. Bouchard, Claude Cooper, Richard S. Evans, Michele K. Gudnason, Vilmundur Kardia, Sharon L. R. Kritchevsky, Stephen B. Levy, Daniel O'Connell, Jeff R. Psaty, Bruce M. van Dam, Rob M. Sims, Mario Arnett, Donna K. Mook-Kanamori, Dennis O. Kelly, Tanika N. Fox, Ervin R. Hayward, Caroline Fornage, Myriam Rotimi, Charles N. Province, Michael A. van Duijn, Cornelia M. Tai, E. Shyong Wong, Tien Yin Loos, Ruth J. F. Reiner, Alex P. Rotter, Jerome I. Zhu, Xiaofeng Bierut, Laura J. Gauderman, W. James Caulfield, Mark J. Elliott, Paul Rice, Kenneth Munroe, Patricia B. Morrison, Alanna C. Cupples, L. Adrienne Rao, Dabeeru C. Chasman, Daniel I. Sung, Yun J. Winkler, Thomas W. de las Fuentes, Lisa Bentley, Amy R. Brown, Michael R. Kraja, Aldi T. Schwander, Karen Ntalla, Ioanna Guo, Xiuqing Franceschini, Nora Lu, Yingchang Cheng, Ching-Yu Sim, Xueling Vojinovic, Dina Marten, Jonathan Musani, Solomon K. Li, Changwei Feitosa, Mary F. Kilpelainen, Tuomas O. Richard, Melissa A. Noordam, Raymond Aslibekyan, Stella Aschard, Hugues Bartz, Traci M. Dorajoo, Rajkumar Liu, Yongmei Manning, Alisa K. Rankinen, Tuomo Smith, Albert Vernon Tajuddin, Salman M. Tayo, Bamidele O. Warren, Helen R. Zhao, Wei Zhou, Yanhua Matoba, Nana Sofer, Tamar Alver, Maris Amini, Marzyeh Boissel, Mathilde Chai, Jin Fang Chen, Xu Divers, Jasmin Gandin, Ilaria Gao, Chuan Giulianini, Franco Goel, Anuj Harris, Sarah E. Hartwig, Fernando Pires Horimoto, Andrea R. V. R. Hsu, Fang-Chi Jackson, Anne U. Kahonen, Mika Kasturiratne, Anuradhani Kuhnel, Brigitte Leander, Karin Lee, Wen-Jane Lin, Keng-Hung Luan, Jian' an McKenzie, Colin A. Meian, He Nelson, Christopher P. Rauramaa, Rainer Schupf, Nicole Scott, Robert A. Sheu, Wayne H. H. Stancakova, Alena Takeuchi, Fumihiko van der Most, Peter J. Varga, Tibor V. Wang, Heming Wang, Yajuan Ware, Erin B. Weiss, Stefan Wen, Wanqing Yanek, Lisa R. Zhang, Weihua Zhao, Jing Hua Afaq, Saima Alfred, Tamuno Amin, Najaf Arking, Dan Aung, Tin Barr, R. Graham Bielak, Lawrence F. Boerwinkle, Eric Bottinger, Erwin P. Braund, Peter S. Brody, Jennifer A. Broeckel, Ulrich Cabrera, Claudia P. Cade, Brian Caizheng, Yu Campbell, Archie Canouil, Mickael Chakravarti, Aravinda Chauhan, Ganesh Christensen, Kaare Cocca, Massimiliano Collins, Francis S. Connell, John M. de Mutsert, Renee de Silva, H. Janaka Debette, Stephanie Dorr, Marcus Duan, Qing Eaton, Charles B. Ehret, Georg Evangelou, Evangelos Faul, Jessica D. Fisher, Virginia A. Forouhi, Nita G. Franco, Oscar H. Friedlander, Yechiel Gao, He Gigante, Bruna Graff, Misa Gu, C. Charles Gu, Dongfeng Gupta, Preeti Hagenaars, Saskia P. Harris, Tamara B. He, Jiang Heikkinen, Sami Heng, Chew-Kiat Hirata, Makoto Hofman, Albert Howard, Barbara V. Hunt, Steven Irvin, Marguerite R. Jia, Yucheng Joehanes, Roby Justice, Anne E. Katsuya, Tomohiro Kaufman, Joel Kerrison, Nicola D. Khor, Chiea Chuen Koh, Woon-Puay Koistinen, Heikki A. Komulainen, Pirjo Kooperberg, Charles Krieger, Jose E. Kubo, Michiaki Kuusisto, Johanna Langefeld, Carl D. Langenberg, Claudia Launer, Lenore J. Lehne, Benjamin Lewis, Cora E. Li, Yize Lim, Sing Hui Lin, Shiow Liu, Ching-Ti Liu, Jianjun Liu, Jingmin Liu, Kiang Liu, Yeheng Loh, Marie Lohman, Kurt K. Long, Jirong Louie, Tin Magi, Reedik Mahajan, Anubha Meitinger, Thomas Metspalu, Andres Milani, Lili Momozawa, Yukihide Morris, Andrew P. Mosley, Thomas H., Jr. Munson, Peter Murray, Alison D. Nalls, Mike A. Nasri, Ubaydah Norris, Jill M. North, Kari Ogunniyi, Adesola Padmanabhan, Sandosh Palmas, Walter R. Palmer, Nicholette D. Pankow, James S. Pedersen, Nancy L. Peters, Annette Peyser, Patricia A. Polasek, Ozren Raitakari, Olli T. Renström, Frida Rice, Treva K. Ridker, Paul M. Robino, Antonietta Robinson, Jennifer G. Rose, Lynda M. Rudan, Igor Sabanayagam, Charumathi Salako, Babatunde L. Sandow, Kevin Schmidt, Carsten O. Schreiner, Pamela J. Scott, William R. Seshadri, Sudha Sever, Peter Sitlani, Colleen M. Smith, Jennifer A. Snieder, Harold Starr, John M. Strauch, Konstantin Tang, Hua Taylor, Kent D. Teo, Yik Ying Tham, Yih Chung Ultterlinden, Andre G. Waldenberger, Melanie Wang, Lihua Wang, Ya X. Bin Wei, Wen Williams, Christine Wilson, Gregory Wojczynski, Mary K. Yao, Jie Yuan, Jian-Min Zonderman, Alan B. Becker, Diane M. Boehnke, Michael Bowden, Donald W. Chambers, John C. Chen, Yii-Der Ida de Faire, Ulf Deary, Ian J. Esko, Tonu Farrall, Martin Forrester, Terrence Franks, Paul W. Freedman, Barry I. Froguel, Philippe Gasparini, Paolo Gieger, Christian Horta, Bernardo Lessa Hung, Yi-Jen Jonas, Jost B. Kato, Norihiro Kooner, Jaspal S. Laakso, Markku Lehtimaki, Terho Liang, Kae-Woei Magnusson, Patrik K. E. Newman, Anne B. Oldehinkel, Albertine J. Pereira, Alexandre C. Redline, Susan Rettig, Rainer Samani, Nilesh J. Scott, James Shu, Xiao-Ou van der Harst, Pim Wagenknecht, Lynne E. Wareham, Nicholas J. Watkins, Hugh Weir, David R. Wickremasinghe, Ananda R. Wu, Tangchun Zheng, Wei Kamatani, Yoichiro Laurie, Cathy C. Bouchard, Claude Cooper, Richard S. Evans, Michele K. Gudnason, Vilmundur Kardia, Sharon L. R. Kritchevsky, Stephen B. Levy, Daniel O'Connell, Jeff R. Psaty, Bruce M. van Dam, Rob M. Sims, Mario Arnett, Donna K. Mook-Kanamori, Dennis O. Kelly, Tanika N. Fox, Ervin R. Hayward, Caroline Fornage, Myriam Rotimi, Charles N. Province, Michael A. van Duijn, Cornelia M. Tai, E. Shyong Wong, Tien Yin Loos, Ruth J. F. Reiner, Alex P. Rotter, Jerome I. Zhu, Xiaofeng Bierut, Laura J. Gauderman, W. James Caulfield, Mark J. Elliott, Paul Rice, Kenneth Munroe, Patricia B. Morrison, Alanna C. Cupples, L. Adrienne Rao, Dabeeru C. Chasman, Daniel I.
Publication Year :
2018
Abstract
Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined similar to 18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 x 10(-8)) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 x 10(-8)). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling MSRA, EBF2).
Details
Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1234439840
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1016.j.ajhg.2018.01.015