A new tool for tracking arsenic poisoning may be hiding in human blood. Researchers at the University of Chicago have developed a DNA methylation-based biomarker that can estimate an individual's arsenic exposure from a blood sample and may predict the risk of serious health consequences, including cancer and cardiovascular disease.
The study, published in the International Journal of Epidemiology, analyzed blood samples from more than 1,100 adults in Bangladesh, where arsenic contamination in well water is a persistent public health crisis. Public health experts estimate that more than 200 million people worldwide are exposed to arsenic through contaminated drinking water, but until now there has been no reliable biological method to track those exposures and understand their full effects on the body.
Using advanced DNA methylation arrays, the research team scanned more than 700,000 sites across the genome, searching for patterns that correlated with arsenic levels measured in participants' urine. They found 1,177 sites significantly associated with arsenic exposure, most of which had never been identified before.
"This was a significant leap in scale and resolution," said lead author James Li, a UChicago MD/Ph.D. student. "Our large sample size and wide range of exposure levels enabled us to identify more sites in the epigenome linked to arsenic exposure than any previous study in adults."
The team went beyond simple correlation. They used a statistical method called Mendelian randomization to determine whether arsenic exposure was actually causing the DNA methylation changes, not merely associated with them. That distinction matters because there is no ethical way to conduct a classic randomized trial with a substance known to harm people.
"Mendelian randomization helped us rule out other variables, allowing us to say not just that arsenic and DNA methylation are associated, but that the way someone's body metabolizes arsenic is likely to cause these changes in DNA methylation," said senior author Brandon Pierce, incoming chair of the Department of Public Health Sciences at UChicago.
From the 1,177 sites identified, the researchers selected 255 to construct a measurable DNA signature. That signature could robustly predict urinary arsenic levels from a blood sample alone, and was also associated with arsenical skin lesions, a visible sign of arsenic toxicity. The biomarker performed consistently across different subgroups within the study population, suggesting it could be broadly applicable.
The researchers say the approach could serve as a model for developing similar epigenetic biomarkers for other environmental toxins, offering a new way to monitor populations at risk and potentially guide interventions before serious disease develops.
