The Epidemiology and Somatic Genomic Pathogenesis of Radon-Related Stroke

氡相关中风的流行病学和体细胞基因组发病机制

基本信息

  • 批准号:
    10580385
  • 负责人:
  • 金额:
    $ 199.53万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-11 至 2026-08-31
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract Although stroke is a major contributor to disability and mortality worldwide, established stroke risk factors have not fully explained the observed burden of or spatial variation in its incidence. Indeed, nearly a third of strokes are cryptogenic, thereby compelling a search for environmental factors that may play an important, but to date, inadequately characterized role in stroke pathogenesis and epidemiology. One such factor—radon—is a naturally occurring, odorless gas generated via decay of radioactive elements in rocks and soils. The gas enters homes through basement and foundation cracks, making unrecognized exposures both ubiquitous and the second-leading, modifiable cause of lung cancer in the US, after smoking. Although radon’s role in lung carcinogenesis is well-known, relatively little is known about its role in the pathogenesis and epidemiology of cerebrovascular disease. Yet extant studies of the radon-stroke association suggest that radon exposure is associated both with pathologic precursors of stroke and incident stroke, itself. Their collective limitations nonetheless leave a substantial gap in the state of the science that could otherwise highlight putative means of reducing radon exposures and their common cerebrovascular sequelae in the US. To fill this gap, we will therefore estimate: [1] pre- and post-mitigation home radon exposures across the US (1986-2018), [2] the association between time-varying home radon exposure and incident stroke, [3] the association between time- varying home radon exposure and clonal hematopoiesis of indeterminate potential (CHIP), and [4] mediation of the radon-stroke association by CHIP. We will do so among a demographically and environmentally diverse group of 194,015 participants in three NHLBI-supported cohorts that have reviewed and approved this proposal. Quantitatively estimating radon exposures and their uncertainties at their accurately geocoded addresses will involve a national, spatiotemporal prediction and two-stage cross-validation based on time-varying, short- and long-term mean, pre- and post-mitigation home radon concentrations; home radon testing statistics / policies; and housing characteristics; plus, time-invariant aerial gamma-radioactivity, geology, and soil features. Estimating radon-stroke and radon-CHIP associations also will involve cohort-specific, multivariable-adjusted, Bayesian, hierarchical, time-to-event and logistic regression accounting for exposure uncertainty and competing mortality, followed by inverse variance-weighted, random-effects meta-analysis. Finally, estimating mediation of the radon-stroke association by CHIP will involve quantifying direct, indirect, and total effects of radon on stroke. The previously unparalleled focus of such estimation on a modifiable risk factor, a plausible mechanism of disease, and a common, clinically and societally burdensome health outcome heretofore ignored by EPA and WHO uniform radon testing and mitigation policies will thereby position the study to help characterize the environmental epidemiology and somatic genomic pathogenesis of stroke and other health outcomes in ways that may lead to the identification of plausible targets for new public health screening and prevention efforts.
项目总结/摘要 虽然中风是世界范围内残疾和死亡的主要原因,但已确定的中风风险因素 没有充分解释所观察到的发病率的负担或空间差异。近三分之一的中风 是隐源的,从而迫使寻找环境因素,可能发挥重要作用,但到目前为止, 在中风发病机制和流行病学中的作用特征不充分。其中一个因素-氡-是 天然存在的、无味的气体,通过岩石和土壤中的放射性元素衰变产生。气体进入 房屋通过地下室和地基裂缝,使未识别的暴露无处不在, 在美国,仅次于吸烟的第二大可改变的肺癌原因。虽然氡在肺中的作用 致癌作用是众所周知的,但对其在肿瘤发病机制和流行病学中的作用知之甚少。 脑血管疾病然而,现有的氡与中风相关性的研究表明, 与中风的病理前兆和中风本身有关。他们的集体局限性 然而,在科学的状态中留下了一个巨大的空白,否则可能会突出假定的方法, 减少氡暴露及其常见的脑血管后遗症。为了填补这一空白,我们将 因此估计:[1]缓解前后美国家庭氡暴露(1986 - 2018),[2] 随时间变化的家庭氡暴露与中风事件之间的关联,[3]时间- 不同的家庭氡暴露和不确定潜力的克隆造血(CHIP),以及[4] 氡与中风的关系。我们将在一个人口和环境多样化的国家中这样做。 NHLBI支持的三个队列中的194,015名参与者已经审查并批准了该提案。 在精确的地理编码地址,对氡暴露量及其不确定性进行定量估算, 涉及全国性的时空预测和基于时变、短期和长期的两阶段交叉验证 长期平均、缓解前后的家庭氡浓度;家庭氡测试统计数据/政策; 和住房特征;加上时不变的航空伽马放射性、地质和土壤特征。 估计氡-中风和氡-CHIP关联还将涉及队列特异性,多变量调整, 贝叶斯、分层、至事件发生时间和逻辑回归解释了暴露不确定性和竞争性 死亡率,然后进行逆方差加权随机效应荟萃分析。最后,估计中介 通过CHIP进行的氡-中风关联将涉及量化氡对中风的直接、间接和总影响。 这种估计以前无与伦比的重点是一个可改变的风险因素,一个合理的机制, 疾病,以及迄今为止被EPA忽视的常见的、临床上和社会上负担沉重的健康结果, 因此,世卫组织统一的氡检测和缓解政策将使研究有助于确定 中风和其他健康结果的环境流行病学和体细胞基因组发病机制, 这可能导致为新的公共卫生筛查和预防工作确定合理的目标。

项目成果

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Eric A. Whitsel其他文献

A comparison of PMsub2.5/sub exposure estimates from different estimation methods and their associations with cognitive testing and brain MRI outcomes
不同估算方法对 PM2.5 暴露估算值的比较及其与认知测试和脑部磁共振成像结果的关联
  • DOI:
    10.1016/j.envres.2024.119178
  • 发表时间:
    2024-09-01
  • 期刊:
  • 影响因子:
    7.700
  • 作者:
    Melinda C. Power;Katie M. Lynch;Erin E. Bennett;Qi Ying;Eun Sug Park;Xiaohui Xu;Richard L. Smith;James D. Stewart;Jeff D. Yanosky;Duanping Liao;Aaron van Donkelaar;Joel D. Kaufman;Lianne Sheppard;Adam A. Szpiro;Eric A. Whitsel
  • 通讯作者:
    Eric A. Whitsel
Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits
西班牙裔/拉丁裔人群的大规模多组学分析确定了心脏代谢特征的基因
  • DOI:
    10.1038/s41467-025-58574-z
  • 发表时间:
    2025-04-11
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Lauren E. Petty;Hung-Hsin Chen;Elizabeth G. Frankel;Wanying Zhu;Carolina G. Downie;Mariaelisa Graff;Phillip Lin;Priya Sharma;Xinruo Zhang;Alyssa C. Scartozzi;Rashedeh Roshani;Joshua M. Landman;Michael Boehnke;Donald W. Bowden;John C. Chambers;Anubha Mahajan;Mark I. McCarthy;Maggie C. Y. Ng;Xueling Sim;Cassandra N. Spracklen;Weihua Zhang;Michael Preuss;Erwin P. Bottinger;Girish N. Nadkarni;Ruth J. F. Loos;Yii-Der Ida Chen;Jingyi Tan;Eli Ipp;Pauline Genter;Leslie S. Emery;Tin Louie;Tamar Sofer;Adrienne M. Stilp;Kent D. Taylor;Anny H. Xiang;Thomas A. Buchanan;Kathryn Roll;Chuan Gao;Nicholette D. Palmer;Jill M. Norris;Lynne E. Wagenknecht;Darryl Nousome;Rohit Varma;Roberta McKean-Cowdin;Xiuqing Guo;Yang Hai;Willa Hsueh;Kevin Sandow;Esteban J. Parra;Miguel Cruz;Adan Valladares-Salgado;Niels Wacher-Rodarte;Jerome I. Rotter;Mark O. Goodarzi;Stephen S. Rich;Alain Bertoni;Leslie J. Raffel;Jerry L. Nadler;Fouad R. Kandeel;Ravindranath Duggirala;John Blangero;Donna M. Lehman;Ralph A. DeFronzo;Farook Thameem;Yujie Wang;Sheila Gahagan;Estela Blanco;Raquel Burrows;Alicia Huerta-Chagoya;Jose C. Florez;Teresa Tusie-Luna;Clicerio González-Villalpando;Lorena Orozco;Christopher A. Haiman;Craig L. Hanis;Rebecca Rohde;Eric A. Whitsel;Alexander P. Reiner;Charles Kooperberg;Yun Li;Qing Duan;Miryoung Lee;Paulina Correa-Burrows;Susan K. Fried;Kari E. North;Joseph B. McCormick;Susan P. Fisher-Hoch;Eric R. Gamazon;Andrew P. Morris;Josep M. Mercader;Heather M. Highland;Jennifer E. Below
  • 通讯作者:
    Jennifer E. Below
PERFORMANCE OF PRESTABILIZATION SHOCK INDEX AS A PREDICTOR OF MORTALITY IN PATIENTS ADMITTED WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: THE ATHEROSCLEROSIS RISK IN COMMUNITIES SURVEILLANCE STUDY
  • DOI:
    10.1016/s0735-1097(18)30780-0
  • 发表时间:
    2018-03-10
  • 期刊:
  • 影响因子:
  • 作者:
    Michael W. Chambers;Eric A. Whitsel;George Stouffer;Amil Shah;Melissa Caughey
  • 通讯作者:
    Melissa Caughey
Association Between Long-term Ambient PMsub2.5/sub Exposure and Cardiovascular Outcomes Among US Hemodialysis Patients
美国血液透析患者长期环境细颗粒物(PM2.5)暴露与心血管结局之间的关联
  • DOI:
    10.1053/j.ajkd.2022.04.008
  • 发表时间:
    2022-11-01
  • 期刊:
  • 影响因子:
    8.200
  • 作者:
    Yuzhi Xi;David B. Richardson;Abhijit V. Kshirsagar;Timothy J. Wade;Jennifer E. Flythe;Eric A. Whitsel;Ana G. Rappold
  • 通讯作者:
    Ana G. Rappold
Association of oil spill cleanup-related hydrocarbon exposure with hypertension and blood pressure in the Gulf Long-term Follow-up Study
海湾长期随访研究中与溢油清理相关的碳氢化合物暴露与高血压和血压的关联
  • DOI:
    10.1016/j.scitotenv.2025.180014
  • 发表时间:
    2025-09-01
  • 期刊:
  • 影响因子:
    8.000
  • 作者:
    Opal P. Patel;Jessie K. Edwards;Anna M. Kucharska-Newton;Eric A. Whitsel;W. Braxton Jackson;Kaitlyn G. Lawrence;Patricia A. Stewart;Mark R. Stenzel;Lawrence S. Engel;Dale P. Sandler
  • 通讯作者:
    Dale P. Sandler

Eric A. Whitsel的其他文献

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{{ truncateString('Eric A. Whitsel', 18)}}的其他基金

Modification of PM-Mediated Arrhythmogenesis in Populations
PM 介导的人群心律失常发生的改变
  • 批准号:
    8279119
  • 财政年份:
    2010
  • 资助金额:
    $ 199.53万
  • 项目类别:
Modification of PM-Mediated Arrhythmogenesis in Populations
PM 介导的人群心律失常发生的改变
  • 批准号:
    8116065
  • 财政年份:
    2010
  • 资助金额:
    $ 199.53万
  • 项目类别:
Modification of PM-Mediated Arrhythmogenesis in Populations
PM 介导的人群心律失常发生的改变
  • 批准号:
    7984809
  • 财政年份:
    2010
  • 资助金额:
    $ 199.53万
  • 项目类别:
Biology Core
生物核心
  • 批准号:
    7718040
  • 财政年份:
    2008
  • 资助金额:
    $ 199.53万
  • 项目类别:
The Environmental Epidemiology of Arrythmogenesis in WHI
WHI 心律失常发生的环境流行病学
  • 批准号:
    7237271
  • 财政年份:
    2003
  • 资助金额:
    $ 199.53万
  • 项目类别:
The Environmental Epidemiology of Arrythmogenesis in WHI
WHI 心律失常发生的环境流行病学
  • 批准号:
    6898232
  • 财政年份:
    2003
  • 资助金额:
    $ 199.53万
  • 项目类别:
The Environmental Epidemiology of Arrythmogenesis in WHI
WHI 心律失常发生的环境流行病学
  • 批准号:
    6799594
  • 财政年份:
    2003
  • 资助金额:
    $ 199.53万
  • 项目类别:
Environmental Epidemiology of Arrhythmogenesis in WHI
WHI 心律失常发生的环境流行病学
  • 批准号:
    6599396
  • 财政年份:
    2003
  • 资助金额:
    $ 199.53万
  • 项目类别:
The Environmental Epidemiology of Arrythmogenesis in WHI
WHI 心律失常发生的环境流行病学
  • 批准号:
    7070576
  • 财政年份:
    2003
  • 资助金额:
    $ 199.53万
  • 项目类别:
Biology Core
生物核心
  • 批准号:
    8126483
  • 财政年份:
  • 资助金额:
    $ 199.53万
  • 项目类别:

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