Blood DNA Marker Predicts Arsenic Exposure and Toxicity Risk

Researchers at the University of Chicago have developed a blood-based DNA marker capable of tracking arsenic exposure and predicting the risk of toxicity. The study, published in the International Journal of Epidemiology, identifies a stable epigenetic signature that may allow health officials to estimate historical exposure and identify individuals at higher risk for chronic illness.

Public health experts estimate that more than 200 million people worldwide are exposed to arsenic through contaminated drinking water. While long-term exposure is known to increase the risk of cardiovascular disease and various cancers, clinicians have lacked a reliable method to track these exposures and understand their biological mechanisms over time.

The research team addressed this gap by analyzing blood samples from over 1,100 adults in Bangladesh, a region where arsenic contamination in well water remains a persistent public health challenge. Using advanced DNA methylation arrays, the scientists scanned more than 700,000 sites across the genome to find patterns that correlated with arsenic levels measured in participants’ urine.

This was a significant leap in scale and resolution. 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.

James Li, PhD, UChicago MD/PhD student and lead author

The team identified 1,177 sites in the genome significantly associated with arsenic exposure. From these findings, the researchers distilled a measurable signature consisting of 255 specific DNA methylation sites. This composite biomarker was found to robustly predict urinary arsenic levels, overall mortality, and the presence of arsenical skin lesions, which are blemishes that serve as a clinically visible sign of arsenic poisoning.

The new marker offers a significant advantage over traditional testing. Because arsenic has a relatively short half-life in the body, measurements taken from urine samples can be subject to fluctuations. The DNA methylation signature, however, provides a more stable and integrative measure of exposure, potentially reflecting the cumulative biological impact over time.

Arsenic has a relatively short half-life in the body after someone drinks contaminated water, so exposure levels measured in urine samples may be liable to fluctuations.

James Li, PhD, UChicago MD/PhD student and lead author

The researchers also found that many of the genome sites most closely associated with arsenic exposure overlapped with sites previously linked to type 2 diabetes, heart disease, and various cancers. While the study does not definitively prove that DNA methylation causes these health effects, the findings suggest a strong link between these epigenetic changes and the development of chronic conditions.

According to the study, the 255-CpG DNAm-based biomarker was highly predictive of urinary arsenic levels, with an r2 of 0.46. It also showed a predictive capacity for arsenical skin-lesion status with an area under the receiver-operating characteristic curve of 0.69.

Senior author Dr. Brandon Pierce noted that the ability of arsenic to modify the epigenome demonstrates how environmental hazards get under the skin to alter fundamental biological functions. The researchers hope this model can be used to develop similar epigenetic biomarkers for other hazardous chemicals, improving early detection and risk stratification for exposed populations worldwide.