The links uncovered through EWAS do not prove that exposure to PCBs or eating more fruits increases a person's risk for getting diabetes. Causation can only be established through longitudinal studies that follow individuals over long periods of time. These links could signify biological differences in how those in the disease population process or deal with various compounds. Further research both in laboratory and population-based studies will be necessary to better understand the nature of these links, notes Butte.
Like scanning genetic microarrays, this mass assessment of environmental risk factors can uncover new links that researchers might not have thought to investigate. Many chemicals and compounds have already been linked to diseases, such as with asbestos and cancer, or vitamin D deficiency and osteoporosis, but by hunting through a broad range of exposures, new links could help lead the way toward better understanding of biological mechanisms behind diseases as well as better treatment and prevention.
"This gives us a clue that we should be studying that particular chemical more closely," Butte says.
This level of study also paves the way for a more unified investigation of environmental and genetic factors in the future. "A lot of these factors do interact with each other," Butte says. But, he cautions, "the interrelationships are incredibly complex." Although Butte does not expect that his team's analytic system will be immediately integrated with genome-wide association studies, he and his colleagues noted in their study that "the results from EWAS can better inform about environmental factors that need to be measured in genetic studies to begin to provide us insight in regards to disease etiology."
Catching up to genetics
Epidemiologists have been investigating the connection between environmental exposures and disease for decades, but, notes Butte, they have depended largely on specific events, such as chemical spills or other disasters, and then looked for spikes in different conditions. Researchers were thus largely stuck investigating environmental factors "the same way genetics was 15 years ago—one by one," he says.
With mass, population-based assessments, that could change, both in the speed and breadth of figuring out environmental roles in disease.
Butte hopes that biotech companies will soon be producing chips to run parallel screening for environmental factors, akin to genetic chips that can now be run rapidly and cheaply. The biological assessments are done using relatively simple analyses of blood and urine samples, which means that, "a lot of these tests could be done on a parallel method," Butte says.
The goal, he says is "to elevate the study of environment to where genetics is."
But the gap between the two fields might be closing anyway, as the number of variables on the genetic side, with epigenetics and other subtler dynamics, seems to grow every day.
In the meantime Butte and his team are already turning EWAS loose on a number of other complex, common conditions, including cholesterol and lipid levels. They are already noticing separate spikes for different environmental exposures between different cholesterol and lipid levels, some of which are "incredibly intriguing," he says.
The results from the new assay underscore the need for more collaboration between environmental and genetic epidemiologists, according to Butte. He and his colleagues concluded in their paper that the findings "demand a rethinking and restructuring" of how genetics and environment are studied in the context of disease risk. "The time is ripe," they wrote, "to usher in 'enviromics'."