{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:51:39Z","timestamp":1753890699126,"version":"3.41.2"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Observational evidence reported that air pollution is a significant risk element for numerous health problems, such as obesity and coronavirus disease 2019 (COVID-19), but their causal relationship is currently unknown. Our objective was to probe the causal relationship between air pollution, obesity, and COVID-19 and to explore whether obesity mediates this association.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We obtained instrumental variables strongly correlated to air pollutants [PM2.5, nitrogen dioxide (NO<jats:sub>2<\/jats:sub>) and nitrogen oxides (NOx)], 9 obesity-related traits (abdominal subcutaneous adipose tissue volume, waist-to-hip ratio, body mass index, hip circumference, waist circumference, obesity class 1-3, visceral adipose tissue volume), and COVID-19 phenotypes (susceptibility, hospitalization, severity) from public genome-wide association studies. We used clinical and genetic data from different public biological databases and performed analysis by two-sample and two-step Mendelian randomization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PM2.5 genetically correlated with 5 obesity-related traits, which obesity class 1 was most affected (beta = 0.38, 95% CI = 0.11 - 0.65, <jats:italic>p<\/jats:italic> = 6.31E-3). NO<jats:sub>2<\/jats:sub> genetically correlated with 3 obesity-related traits, which obesity class 1 was also most affected (beta = 0.33, 95% CI = 0.055 - 0.61, <jats:italic>p<\/jats:italic> = 1.90E-2). NOx genetically correlated with 7 obesity-related traits, which obesity class 3 was most affected (beta = 1.16, 95% CI = 0.42-1.90, <jats:italic>p<\/jats:italic> = 2.10E-3). Almost all the obesity-related traits genetically increased the risks for COVID-19 phenotypes. Among them, body mass index, waist circumference, hip circumference, waist-to-hip ratio, and obesity class 1 and 2 mediated the effects of air pollutants on COVID-19 risks (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). However, no direct causal relationship was observed between air pollution and COVID-19.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study suggested that exposure to heavy air pollutants causally increased risks for obesity. Besides, obesity causally increased the risks for COVID-19 phenotypes. Attention needs to be paid to weight status for the population who suffer from heavy air pollution, as they are more likely to be susceptible and vulnerable to COVID-19.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1221442","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T13:25:22Z","timestamp":1696512322000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The causal relationship between air pollution, obesity, and COVID-19 risk: a large-scale genetic correlation 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