Long-term PM2.5 exposure is associated with prevalent metabolic syndrome and subsequent cardiovascular disease risk among individuals with metabolic syndrome, particularly among genetically susceptible individuals, with DNA methylation potentially serving as an epigenetic link in these associations.
Higher long-term PM2.5 exposure was associated with greater odds of prevalent metabolic syndrome in the UK Biobank cohort.
Among individuals with metabolic syndrome, higher long-term PM2.5 exposure was associated with elevated incident cardiovascular disease risk.
PM2.5 exposure showed significant additive interaction with polygenic risk score (PRS) for metabolic syndrome on MetS risk.
PM2.5 exposure showed significant additive interaction with polygenic risk score (PRS) for CVD on cardiovascular disease risk among MetS individuals.
Summary-data-based Mendelian randomization (SMR) analyses identified PM2.5-associated CpG methylation sites linked to metabolic syndrome and cardiovascular disease.
The CpG site cg13235717 near the SFN gene emerged as a key epigenetic locus across both metabolic syndrome and cardiovascular disease phenotypes.
DNA methylation was identified as a potential epigenetic link between long-term PM2.5 exposure and cardiometabolic disease risk.
This research suggests that breathing air with higher levels of fine particulate matter (PM2.5) pollution over the long term is associated with a higher likelihood of having metabolic syndrome — a cluster of conditions including high blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol levels — and, among people who already have metabolic syndrome, a higher risk of developing cardiovascular disease. Using data from nearly 325,000 UK Biobank participants, the study found that the associations, while modest in size (about 4% increased odds or risk per unit of PM2.5 increase), were statistically significant and consistent. Importantly, this research suggests that people who are genetically predisposed to metabolic syndrome or cardiovascular disease face a compounded risk when also exposed to high levels of PM2.5. The combined effect of genetic risk and air pollution was greater than what would be expected if their effects simply added together, indicating a synergistic relationship. This means that individuals with high genetic susceptibility may be especially vulnerable to the harmful cardiometabolic effects of air pollution. The study also investigated how PM2.5 might affect health at a molecular level, finding several specific DNA methylation sites — chemical tags on DNA that can turn genes on or off — that appear to link air pollution exposure to metabolic syndrome and cardiovascular disease. One site in particular, near a gene called SFN, appeared relevant to both conditions, pointing toward a possible shared biological pathway. These findings highlight the importance of reducing air pollution exposure, particularly for genetically at-risk populations, and open avenues for future research into epigenetic mechanisms connecting environmental exposures to cardiometabolic disease.
Li Z, Huang H, Chen J, Qin Q, Ruan H, Zhang T, et al.. (2026). Associations of long-term PM2.5 exposure and genetic susceptibility with prevalent metabolic syndrome and subsequent cardiovascular disease risk: A UK Biobank cohort study.. Ecotoxicology and environmental safety. https://doi.org/10.1016/j.ecoenv.2026.120802