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This study evaluates both individual and joint effects of long-term air pollutant exposure and polygenic risk on incident CVD in a UK Biobank prospective cohort of 460,572 participants, using Cox models and interaction assessments. Results indicate independent and significant synergistic effects across pollutants and persisting patterns below WHO guidelines, supporting air quality reassessment and genetics-informed mitigation.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/synergistic-effects-of-genetic-susceptibility-and-air-pollution-on-cardiovascular-disease-article/454026/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/synergistic-effects-of-genetic-susceptibility-and-air-pollution-on-cardiovascular-disease-article/454026.png","ImageObject",300,407,{"name":92,"@type":93},"Jake","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What question does the study address about air pollution and genetic susceptibility?","Question",{"text":112,"@type":113},"It investigates how genetic susceptibility and long-term air pollutant exposure jointly influence incident cardiovascular disease risk, with emphasis on interaction effects on additive and multiplicative scales.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was the study conducted?",{"text":117,"@type":113},"Using a prospective cohort of 460,572 participants from the UK Biobank, the study estimated hazard ratios for CVD associated with PM2.5, PM10, NO2, and NOX and constructed a polygenic risk score. Interaction between polygenic risk and air pollution was then assessed.",{"name":119,"@type":110,"acceptedAnswer":120},"What did the study find about the combined effect?",{"text":121,"@type":113},"The results suggest reevaluating air quality standards and indicate that genetic profiling could help identify subpopulations that would benefit most from air pollution mitigation strategies.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},454026,1790794702,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},962084928904,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","American Journal of Preventive Cardiology 25 (2026) 101381  \nContents lists available at ScienceDirect  \nAmerican Journal of Preventive Cardiology  \njournal [homepage:](homepage: www.journals.elsevier.com/american-journal-of-preventive-cardiology)[ www.journals.elsevier.com/american-journal-of-preventive-cardiology](homepage: www.journals.elsevier.com/american-journal-of-preventive-cardiology)  \n| Synergistic effects of genetic susceptibility and air pollution on cardiovascular disease |  |  | |\n| --- | --- | --- | --- |\n| Yun-Jiu Chenga,1, Li-Juan Liu b,c,1, Su-Hua Wu b,c,1, Li-Chun Wang b,c,1, Hai Denga,\u003Cbr>Hui-Qiang Wei a, Wei-Dong Lina, Xian-Hong Fanga, Yi-Jian Liaod, Shu-Lin Wu a, Yu-Mei Xuea,*, Yue-Dong Mab,c,*, Yang Wu b,c,*\u003Cbr>a Department of Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China\u003Cbr>b Department of Cardiology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China\u003Cbr>c NHC Key Laboratory of Assisted Circulation, Sun Yat-Sen University, Guangzhou, China d The First Clinical Medical College, Guangdong Medical University, Zhanjiang, China |  |  |  |\n| A R T I C L E I N F O |  | A B S T R A C T |  |\n| Keywords: Air pollution Genetic susceptibility\u003Cbr>Cardiovascular disease Polygenic risk score |  | Background: Although both genetic susceptibility and air pollution are established risk factors for cardiovascular disease (CVD), evidence for their interaction, particularly on the additive scale, remains limited and inconclusive. We aimed to investigate the individual and joint effects of long-term exposure to air pollutants and polygenic risk on incident CVD.\u003Cbr>Methods: In a prospective cohort of 460,572 participants from the UK Biobank, we estimated hazard ratios (HRs) for CVD associated with particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOX) using Cox models. A polygenic risk score (PRS) for CVD was constructed, and additive and multiplicative interactions between PRS and air pollution were assessed.\u003Cbr>Results: Over a median follow-up of 11.92 years, 48,690 incident CVD cases occurred. Both a higher genetic risk and increased air pollution exposure were independently associated with elevated CVD risk. Notably, a significant synergistic effect was observed. Compared to participants with low genetic risk and low pollution exposure, those with high genetic risk and high exposure faced the greatest hazard, with HRs of 1.76 (1.68–1.84) for PM2.5, 1.74 (1.66–1.83) for PM10, 1.82 (1.73–1.91) for NO2, and 1.81 (1.73–1.90) for NOx. These associations persisted at concentrations below WHO air quality guidelines and were robust across a series of sensitivity analyses. Conclusions: Our findings call for a reevaluation of air quality standards and indicate that genetic profiling could identify subpopulations that would derive the greatest benefit from air pollution mitigation strategies. |  |\n\nCentral illustration.  \n1. Introduction  \nCardiovascular disease (CVD) remains a global public health concern, accounting for a substantial proportion of morbidity and mortality worldwide [1,2]. Despite advancements in prevention and treatment strategies, the increasing prevalence of CVD underscores the urgency to identify and address modifiable risk factors. A crucial aspect of this endeavor lies in understanding the intricate interplay between  \n* Corresponding authors.  \nE-mail addresses: [xymgdci@163.com](xymgdci@163.com) (Y.-M. Xue), [maydong@mail.sysu.edu.cn](maydong@mail.sysu.edu.cn) (Y.-D. Ma), [wuyang39@mail2.sysu.edu.cn](wuyang39@mail2.sysu.edu.cn) (Y. Wu).  \n1 These authors contributed equally to this work.  \n[https://doi.org/10.1016/j.ajpc.2025.101381](https://doi.org/10.1016/j.ajpc.2025.101381)  \nReceived 14 October 2025; Received in revised form 5 December 2025; Accepted 10 December 2025  \nAvailable online 11 December 2025  \n2666-6677/© 2025 The Authors. Publ","cbCaieMjahbnUEkd","https://ap.wps.com/l/cbCaieMjahbnUEkd","pdf",2655778,"English","# Introduction\n# Methods\n## Study design and participant cohort","[{\"question\":\"What question does the study address about air pollution and genetic susceptibility?\",\"answer\":\"It investigates how genetic susceptibility and long-term air pollutant exposure jointly influence incident cardiovascular disease risk, with emphasis on interaction effects on additive and multiplicative scales.\"},{\"question\":\"How was the study conducted?\",\"answer\":\"Using a prospective cohort of 460,572 participants from the UK Biobank, the study estimated hazard ratios for CVD associated with PM2.5, PM10, NO2, and NOX and constructed a polygenic risk score. Interaction between polygenic risk and air pollution was then assessed.\"},{\"question\":\"What did the study find about the combined effect?\",\"answer\":\"The results suggest reevaluating air quality standards and indicate that genetic profiling could help identify subpopulations that would benefit most from air pollution mitigation strategies.\"}]","Synergistic effects of genetic susceptibility and air pollution on cardiovascular disease - Article | PDF",1790740043,25]