Медицинская библиотека · medRxiv : the preprint server for health sciences · 2025
Large-Scale Gene-Smoking Interactions and Fine Mapping Study Identifies Multiple Novel Blood Pressure Loci in over 1 Million Individuals.
Zhang Mengyu, Brown Michael R, Bentley Amy R, Winkler Thomas W, Noordam Raymond, Nagarajan Pavithra, Guo Bohong, Lee Songmi, Schwander Karen, Wang Wenyi, Westerman Kenneth, O'Connell Jeffrey R, Ammous Farah, Argoty-Pantoja Anna D, Bartz Traci M, Batini Chiara, Boua Palwende R, Cordell Heather J, Díez-Ahijado Laia, Dimitrov Latchezar, Do Anh N, Du Jiawen, Feitosa Mary F, Giri Ayush, Giulianini Franco, Gudmundsdottir Valborg, Guo Xiuqing, Harris Sarah E, Hasbani Natalie R, Herold Janina M, Hikino Keiko, Hofer Edith, Hsu Fang-Chi, Jackson Anne U, Kho Minjung, Kraja Aldi T, Lyytikäinen Leo-Pekka, Meirhaeghe Aline, Muntaner Manon, Nakatochi Masahiro, Nardone Giuseppe Giovanni, Nutile Teresa, Palmer Nicholette D, Pecori Alessandro, Rao Varun S, Rauramaa Rainer, Sanghvi Mihir M, Santin Aurora, Shen Botong, Stringham Heather M, Takeuchi Fumihiko, Tan Ye An, Tang Jingxian, Thériault Sébastien, Trofimova Olga, Trompet Stella, van der Most Peter J, Wang Ya Xing, Wang Zhe, Wang Yujie, Ware Erin B, Weiss Stefan, Wickremasinghe Ananda Rajitha, Yu Chenglong, Zhu Wanying, Ansari Md Abu Yusuf, Anugu Pramod, Banas Bernhard, Barr R Graham, Basnet Til B, Boerwinkle Eric, Böger Carsten A, Breyer Max, Broeckel Ulrich, Bryant Luke, Cade Brian, Camarda Silvia, Cennamo Pasqualina, Checkley William, Chee Miao-Li, Chen Guanjie, Coley Kayesha, Collins Stacey D, de Borst Martin H, de Las Fuentes Lisa, Deary Ian J, Dupont Charles T, Enzinger Christian, Faquih Tariq, Faul Jessica D, Silva Lilian Fernandes, Gauthier Victoria, Gepner Adam D, Gorski Mathias, Grabe Hans Jörgen, Graff Mariaelisa, Gu Charles C, He Jiang, Heikkinen Sami, Hidalgo Bertha, Highland Heather M, Hixson James E, Hood Michelle M, Hunt Steven C, Irvin Marguerite Ryan, Isono Masato, Kähönen Mika, Kardia Sharon L R, Karvonen-Gutierrez Carrie A, Kasturiratne Anuradhani, Katsuya Tomohiro, Kaufman Joel D, Koistinen Heikki A, Komulainen Pirjo, Krämer Bernhard K, Launer Lenore J, Leonard Hampton, Levy Daniel, Lifelines Cohort Study, Liu Jianjun, Marques-Vidal Pedro, Martinez-Perez Angel, Matsuda Koichi, McNeil John J, Milaneschi Yuri, Miranda J Jaime, Morrison John L, Nalls Michael, Ng Maggie Cy, Nolte Ilja M, Norris Jill M, Oravilahti Anniina, Patki Amit, Petty Lauren E, Peyser Patricia A, Pianigiani Giulia, Raffield Laura M, Raitakari Olli T, Ramsay Michele, Rice Ken M, Ridker Paul M, Risch Lorenz, Risch Martin, Ruggiero Daniela, Ruiz-Narvaez Edward A, Russ Tom C, Sabanayagam Charumathi, Vaitinadin Nataraja Sarma, Schmidt Reinhold, Scott Laura J, Singh Surina, Sitlani Colleen M, Smit Roelof A J, Smith Jennifer A, Sun Quan, Tai E Shyong, Taylor Kent D, Tesolin Paola, Tham Yih Chung, Biobank Japan Project, Tinashe Chikowore, van Dam Rob M, Vaucher Julien, Völker Uwe, Wang Chaolong, Wilson Otis D, Wong Tien-Yin, Xu Jianzhao, Yamamoto Ken, Yao Jie, Yokota Mitsuhiro, Young Kristin L, Zimmermann Martina E, Amouyel Philippe, Below Jennifer E, Bergmann Sven, Bernabe-Ortiz Antonio, Bierut Laura, Boehnke Michael, Bowden Donald W, Brandenburg Jean-Tristan, Chasman Daniel I, Cheng Ching-Yu, Ciullo Marina, Concas Maria Pina, Conen David, Cox Simon R, Dauchet Luc, de Silva Hithanadura Janaka, Dörr Marcus, Edwards Todd L, Fox Ervin R, Franceschini Nora, Freedman Barry I, Girotto Giorgia, Gudnason Vilmundur, Harlow Sioban D, Heid Iris M, Hung Adriana M, Ichihara Sahoko, Jaquish Cashell E, John Catherine, Jonas Jost B, Jukema J Wouter, Kato Norihiro, Keavney Bernard D, Kelly Tanika N, Laakso Markku, Lacaze Paul, Lakka Timo, Lee Seunggeun, Lehtimäki Terho, Liu Ching-Ti, Loos Ruth J F, North Kari E, Penninx Brenda, Province Michael A, Psaty Bruce M, Redline Susan, Rosendaal Frits R, Rotimi Charles N, Rotter Jerome I, Sabater-Lleal Maria, Schmidt Helena, Sim Xueling, Snieder Harold, Spedicati Beatrice, Stark Klaus J, Terao Chikashi, Wagenknecht Lynne E, Weir David R, Zhao Wei, Zhu Xiaofeng, Munroe Patricia B, Sun Yan V, Gauderman James, Manning Alisa K, Fornage Myriam, Aschard Hugues, Wang Heming, de Vries Paul S, Wang Gao, Rao Dabeeru C, Morrison Alanna C, Chen Han
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Аннотация
Cigarette smoking influences blood pressure (BP) levels. Studying and accounting for potential gene-smoking interactions can help discover novel loci and provide insights into biological pathways for smoking-associated BP regulation. We conducted a genome-wide association meta-analysis involving 1,188,241 individuals from 66 studies in five ancestry groups, analyzing systolic BP, diastolic BP, and pulse pressure while considering interactions between genetic variants and three smoking exposures: smoking status, cigarettes per day, and pack years. These analyses identified twelve novel loci for BP at genome-wide significance ( P < 5 × 10 - 9 ), and highlighted biological processes including tight junction integrity, mitochondrial health, vascular relaxation, and endothelial function. In smoking status-stratified analyses, smoking modifies the genetic effect of six variants on BP. To prioritize likely causal, we developed and applied SuSiEgxe, a fine-mapping method based on a two-degree-of-freedom joint test using gene-environment interaction summary statistics. Fine-mapped loci uncovered immune-related pathway for smoking-associated BP regulation.
Для цитирования: Zhang Mengyu, Brown Michael R, Bentley Amy R, Winkler Thomas W, Noordam Raymond, Nagarajan Pavithra, Guo Bohong, Lee Songmi, Schwander Karen, Wang Wenyi, Westerman Kenneth, O'Connell Jeffrey R, Ammous Farah, Argoty-Pantoja Anna D, Bartz Traci M, Batini Chiara, Boua Palwende R, Cordell Heather J, Díez-Ahijado Laia, Dimitrov Latchezar, Do Anh N, Du Jiawen, Feitosa Mary F, Giri Ayush, Giulianini Franco, Gudmundsdottir Valborg, Guo Xiuqing, Harris Sarah E, Hasbani Natalie R, Herold Janina M, Hikino Keiko, Hofer Edith, Hsu Fang-Chi, Jackson Anne U, Kho Minjung, Kraja Aldi T, Lyytikäinen Leo-Pekka, Meirhaeghe Aline, Muntaner Manon, Nakatochi Masahiro, Nardone Giuseppe Giovanni, Nutile Teresa, Palmer Nicholette D, Pecori Alessandro, Rao Varun S, Rauramaa Rainer, Sanghvi Mihir M, Santin Aurora, Shen Botong, Stringham Heather M, Takeuchi Fumihiko, Tan Ye An, Tang Jingxian, Thériault Sébastien, Trofimova Olga, Trompet Stella, van der Most Peter J, Wang Ya Xing, Wang Zhe, Wang Yujie, Ware Erin B, Weiss Stefan, Wickremasinghe Ananda Rajitha, Yu Chenglong, Zhu Wanying, Ansari Md Abu Yusuf, Anugu Pramod, Banas Bernhard, Barr R Graham, Basnet Til B, Boerwinkle Eric, Böger Carsten A, Breyer Max, Broeckel Ulrich, Bryant Luke, Cade Brian, Camarda Silvia, Cennamo Pasqualina, Checkley William, Chee Miao-Li, Chen Guanjie, Coley Kayesha, Collins Stacey D, de Borst Martin H, de Las Fuentes Lisa, Deary Ian J, Dupont Charles T, Enzinger Christian, Faquih Tariq, Faul Jessica D, Silva Lilian Fernandes, Gauthier Victoria, Gepner Adam D, Gorski Mathias, Grabe Hans Jörgen, Graff Mariaelisa, Gu Charles C, He Jiang, Heikkinen Sami, Hidalgo Bertha, Highland Heather M, Hixson James E, Hood Michelle M, Hunt Steven C, Irvin Marguerite Ryan, Isono Masato, Kähönen Mika, Kardia Sharon L R, Karvonen-Gutierrez Carrie A, Kasturiratne Anuradhani, Katsuya Tomohiro, Kaufman Joel D, Koistinen Heikki A, Komulainen Pirjo, Krämer Bernhard K, Launer Lenore J, Leonard Hampton, Levy Daniel, Lifelines Cohort Study, Liu Jianjun, Marques-Vidal Pedro, Martinez-Perez Angel, Matsuda Koichi, McNeil John J, Milaneschi Yuri, Miranda J Jaime, Morrison John L, Nalls Michael, Ng Maggie Cy, Nolte Ilja M, Norris Jill M, Oravilahti Anniina, Patki Amit, Petty Lauren E, Peyser Patricia A, Pianigiani Giulia, Raffield Laura M, Raitakari Olli T, Ramsay Michele, Rice Ken M, Ridker Paul M, Risch Lorenz, Risch Martin, Ruggiero Daniela, Ruiz-Narvaez Edward A, Russ Tom C, Sabanayagam Charumathi, Vaitinadin Nataraja Sarma, Schmidt Reinhold, Scott Laura J, Singh Surina, Sitlani Colleen M, Smit Roelof A J, Smith Jennifer A, Sun Quan, Tai E Shyong, Taylor Kent D, Tesolin Paola, Tham Yih Chung, Biobank Japan Project, Tinashe Chikowore, van Dam Rob M, Vaucher Julien, Völker Uwe, Wang Chaolong, Wilson Otis D, Wong Tien-Yin, Xu Jianzhao, Yamamoto Ken, Yao Jie, Yokota Mitsuhiro, Young Kristin L, Zimmermann Martina E, Amouyel Philippe, Below Jennifer E, Bergmann Sven, Bernabe-Ortiz Antonio, Bierut Laura, Boehnke Michael, Bowden Donald W, Brandenburg Jean-Tristan, Chasman Daniel I, Cheng Ching-Yu, Ciullo Marina, Concas Maria Pina, Conen David, Cox Simon R, Dauchet Luc, de Silva Hithanadura Janaka, Dörr Marcus, Edwards Todd L, Fox Ervin R, Franceschini Nora, Freedman Barry I, Girotto Giorgia, Gudnason Vilmundur, Harlow Sioban D, Heid Iris M, Hung Adriana M, Ichihara Sahoko, Jaquish Cashell E, John Catherine, Jonas Jost B, Jukema J Wouter, Kato Norihiro, Keavney Bernard D, Kelly Tanika N, Laakso Markku, Lacaze Paul, Lakka Timo, Lee Seunggeun, Lehtimäki Terho, Liu Ching-Ti, Loos Ruth J F, North Kari E, Penninx Brenda, Province Michael A, Psaty Bruce M, Redline Susan, Rosendaal Frits R, Rotimi Charles N, Rotter Jerome I, Sabater-Lleal Maria, Schmidt Helena, Sim Xueling, Snieder Harold, Spedicati Beatrice, Stark Klaus J, Terao Chikashi, Wagenknecht Lynne E, Weir David R, Zhao Wei, Zhu Xiaofeng, Munroe Patricia B, Sun Yan V, Gauderman James, Manning Alisa K, Fornage Myriam, Aschard Hugues, Wang Heming, de Vries Paul S, Wang Gao, Rao Dabeeru C, Morrison Alanna C, Chen Han. Large-Scale Gene-Smoking Interactions and Fine Mapping Study Identifies Multiple Novel Blood Pressure Loci in over 1 Million Individuals.. medRxiv : the preprint server for health sciences. 2025. DOI: 10.1101/2025.10.06.25337440.
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