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2024
article
A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure
S. Debette, Annette Peters, J.M. Norris, M. Kähönen, Yechiel Friedlander, J.F. Chai, Patricia A. Peyser, Lisa R. Yanek, Yih Chung Tham, Brian E. Cade, Fernando Pires Hartwig, Yanmei Lu, Albert V. Smith, Hugues Aschard, F. Giulianini, Paul M. Ridker, Hua Tang, John M. Starr, Alison D. Murray, B. Gigante, Ilaria Gandin, Michael R. Brown, Jasmin Divers, Harold Snieder, Maris Alver, Tibor V. Varga, Rajkumar Dorajoo, Yao Jia, T. Alfred, J.S. Pankow, Roby Joehanes, Oscar H. Franco, Olli T. Raitakari, J. Liu, C.-T. Liu, Arnab Chakravarti, Arthur A. Campbell, Ozren Polašek, Adesola Ogunniyi, Stella Aslibekyan, Tom Mosley, Lili Milani, H.R. Warren, C.M. Sitlani, Xueling Sim, Ankit Mahajan, Karen Schwander, Makoto Hirata, Dan E. Arking, Tomohiro Katsuya, Yu Wang, Lisa de las Fuentes, Y. Li, Sandosh Padmanabhan, H.A. Koistinen, Peter S. Braund, Pirjo Komulainen, Fang‐Chi Hsu, Kari E. North, H. Meian, K. Christensen, Lenore J. Launer, Michiaki Kubo, Benjamin Lehne, Mariacristina Cocca, Han Gao, Kurt K. Lohman, K.-H. Lin, N.D. Kerrison, C.E. Lewis, E.P. Bottinger, Antonietta Robino, Paul L. Munson, Colin A. McKenzie, Peter J. van der Most, C.-Y. Cheng, William R. Scott, Najaf Amin, Yukihide Momozawa, Weiwei Zhao, Won‐Jae Lee, Sami Heikkinen, Marzyeh Amini, Salman M. Tajuddin, M.A. Richard, Thomas Meitinger, P.J. Schreiner, Erin B. Ware, John Connell, Nora Franceschini, Peter Sever, A.R.V.R. Horimoto, Virginia Fisher, Alisa K. Manning, C. Charles Gu, R. Graham Barr, R.A. Scott, Johanna Kuusisto, Konstantin Strauch, M Dörr, Xiuqing Guo, G. Ehret, W. Palmas, Lawrence F. Bielak, Alena Stančáková, Yu Caizheng, Chiea Chuen Khor, Barbara V. Howard, W. Zhang, Steven C. Hunt, Mike A. Nalls, B. Kühnel, Yik Ying Teo, Prasoon Gupta, Treva Rice, Mary F. Feitosa, H. Wang, Anne Jackson, Dazhang Gu, Tamar Sofer, Mathilde Boissel, Igor Rudan, Charles Kooperberg, Sarah E. Harris, Jennifer A. Smith, Shenghuang Lin, Chew‐Kiat Heng, Roelande Hofman, Chenyao Li, Tin Aung, Lynda M. Rose, Jim Kaufman, Tamara B. Harris, Mickaël Canouil, Jennifer G. Robinson, N.G. Forouhi, Tuomo Rankinen, Andres Metspalu, K.D. Taylor, Saskia P. Hagenaars, Εvangelos Εvangelou, Jessica D. Faul, Jing Hua Zhao, Frida Renström, K. Liu, Qing Duan, Saima Afaq, Babatunde Salako, Ganesh Chauhan, Amy R. Bentley, Anuj Goel, H.J. de Silva, Nana Matoba, Ιωάννα Ντάλλα, Wanqing Wen, Anuradhani Kasturiratne, Jaclyn S. Long, Tin Louie, Nicole Schupf, Yong Zhou, José Eduardo Krieger, Claudia P. Cabrera, Christopher P. Nelson, S.K. Musani, Nancy L. Pedersen, Chuan Gao, Charumathi Sabanayagam, Thomas W. Winkler, Traci M. Bartz, Ubaydah Nasri, Marie Loh, Bamidele O. Tayo, W.H.H. Sheu, Claudia Langenberg, Sung‐Hoon Lim, X. Chen, Renée de Mutsert, J.A. Brody, Raymond Noordam, A.T. Kraja, Reedik Mägi, Dina Vojinović, Rainer Rauramaa, Jiang He, M.R. Irvin, Ulrich Broeckel, Carl D. Langefeld, Jian’an Luan, T.O. Kilpeläinen, Carsten Oliver Schmidt, Eric Boerwinkle, Fumihiko Takeuchi, A.P. Morris, Woon‐Puay Koh, Charles B. Eaton, Karin Leander, Mariaelisa Graff, Sudha Seshadri, A.E. Justice, J. Marten, K. Sandow
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Résumé fourni par la source
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 ~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).
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Sujets associés
Genetic Associations and EpidemiologyNutrition, Genetics, and Disease