Practicing the same method as geneticists use to study genetic factors for disease, researchers at Stanford University successfully used an environment-wide association study (EWAS) to study environmental factors for disease. The report appeared in the May 20 issue of PLoS, a journal of The Public Library of Science.

The researchers turned to EWAS as a way to study environmental risk factors because genetic-wide association studies have been so effective in recognizing genetic risk factors, says Atul Butte, researcher and assistant professor of pediatrics and medical informatics at Stanford University.

"Environmental factors haven't gotten the same kind of respect that the genetics field has," he says, pointing out that environmental factors are much stronger in affecting the development of Type 2 diabetes. "Environmental causes are certainly stronger. We wouldn't have the increase rate of Type 2 diabetes [that we do] from genetics because our genes aren't changing fast enough."

Butte and his team focused on Type 2 diabetes, which is a "public health menace," he says.

The scientists gathered public data from the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey, which looked at environmental risk factors such as nutrients, vitamins, allergens, pollutants and pesticides.

The data was all adjusted to account for factors including age, gender, body mass index and socioeconomic status.

Out of 226 environmental factors, the researchers found Type 2 diabetes association with tocopherol, a form of vitamin E, heptachlor epoxide, a pesticide that was outlawed in the 1980s, and polychlorinated biphenyls (PCBs), which are chemicals that were banned in the 1970s because of their association with cancer.

Edward McCabe, past president of American Society of Human Genetics and current physician-in-chief at Mattel Children's Hospital at UCLA, says the fact that the researchers were able to study 226 factors is "impressive."

Butte says he was "absolutely" surprised by the findings, especially the vitamin E association with Type 2 diabetes.

The researchers were also able to confirm that vitamin D and beta carotene possess protective properties. And they didn't even look at some factors, which have been proven as having an effect on Type 2 diabetes development.

"The most obvious factors are still always diet and exercise," Butte says. "What you eat still plays the largest role [in developing Type 2 diabetes]. We knew we would find some of those, so we didn't even look at those...This doesn't mean all of a sudden you can stop that diet or stop trying to lose weight."

In order to determine whether certain environmental factors were associated with Type 2 diabetes, the researchers looked at what elevated levels of certain factors were also found in people with diabetes, says Butte. He points out that this was not a causal study; these findings don't mean a certain factor causes diabetes.

But when it comes to explaining why a certain factor is associated with Type 2 diabetes, Butte says right now, it's purely speculation. And the researchers can't begin to explain why vitamin E may be associated with the disease.

"For us, vitamin E is the most puzzling. It's an antioxidant," he says. "[Heptachlor] was banned in the 80s because of its association with cancer. It's known to play a role in affecting cellular systems. Perhaps it's playing the same kind of role here."

What Butte and his researchers are most excited about is what these findings mean for the future of environmental risk factor testing. In the past, it has been difficult to study individual risk factors, but using EWAS will allow scientists to study factors across the board.

"We know we can apply the same method to other disorders - cholesterol, lipid abnormality," he says. "The next step is to think about the biology...The next step is a longitudinal study. It would be to [look at] the elevation in factors to see how long it would take for a person to get diabetes...and figure out the causal link."

"I hope this paper brings the study of environmental risk factors up to where genetics and genomics have been in the past 10 to 15 years," Butte says.

McCabe thinks the success of this research is extremely promising when it comes to factors that cause disease, even though he emphasizes that this study was merely an association study.

He is part of a national children's study that looks at environmental and genetic factors that influence the health of children.

"This is a very important study in paving the way for future studies looking at complex causation, not just on nutrition or environmental exposure, not just genetics, but the ability to put them all together," he says.