Researchers at Harvard Medical School announced on April 6 the results of a large-scale study examining how various environmental and lifestyle exposures, collectively known as the exposome, influence disease risk. The findings were published March 18 in Nature Medicine.
The research highlights that while genetics have long been studied for their role in common diseases such as cancer, diabetes, and heart disease, external factors like pollution, infections, diet, and lifestyle also play a significant part. By analyzing more than 100,000 associations between exposures and health outcomes using survey data from U.S. populations over two decades, the team found that individual exposures had only moderate effects but their combined impact was greater.
According to the study authors, considering multiple exposures together increased their explanatory power for health outcomes. For example, a combination of twenty different exposures explained up to 43 percent of variation in triglyceride levels—a key heart disease risk factor—whereas single exposures typically explained less than one percent of variation across hundreds of outcomes. "On the whole, there's no smoking gun; every exposure seems to matter a little bit, and exposures matter more when you consider them in aggregate," said Patel.
Senior author Arjun (Raj) Manrai said many previous studies focused on single exposure-outcome relationships but often produced conflicting results. "We really wanted to build a robust, large-scale compendium of these associations for the exposome," Manrai said.
The team used data from the National Health and Nutrition Examination Survey conducted by the Centers for Disease Control and Prevention over twenty years. They identified more than 5,600 statistically significant associations among 619 environmental exposures and 305 health outcomes.
Looking ahead, Patel and Manrai plan to expand their research to include even more types of environmental factors and investigate how early-life exposures affect later health. Their dataset is available online through The Phenome-Exposure Atlas of Health and Disease Risk so other researchers can explore these connections further. "Large-scale analyses like this are an agnostic, systematic way of generating hypotheses... We're zooming out to figure out where to zoom back in," Manrai said.
