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. 

New leads
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'."

10 Comments

1. 1. billsmith 02:16 PM 5/21/10

   
   The association of diabetes with high gamma-tocopherol is an odd one. Perhaps diabetic people in the NHANES survey (from which Butte took the data) were more likely to report eating foods fried in vegetable oils like corn and soybean (McDonalds anyone?). These foods are high in gamma-tocopherol. But as the article said, don't stop eating it from healthy sources, as it may be good for the heart as part of a low-fat diet.
   
   http://lpi.oregonstate.edu/ss03/vitamine.html
   http://www.annals.org/content/143/2/116.full
   http://www.ajcn.org/cgi/reprint/74/6/714.pdf
   
   This study from Europe (where alpha-tocopherol is not just from supplements) found low levels of alpha-tocopherol and beta-carotene to be associated with diabetes.
   
   http://www.ncbi.nlm.nih.gov/pubmed/18985315
   
   As for the small association between diabetes and low beta-carotene levels, in it has been noticed before. But further studies have failed to show that eating more beta-carotene will prevent diabetes. Oh well...carrots can't cure everything.
   
   http://www.ncbi.nlm.nih.gov/pubmed/19662379
   
   Eating more yellow-orange vegetables couldn't do any harm, though, as a vegetable-rich diet is good insurance against other dieases (and the body will store away or excrete any excess beta-carotene).
   

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2. 2. hankroberts 05:20 PM 5/21/10

   Hm. From the Wikipedia article on PCBs:
   
   "Manufacture peaked in the 1960s, by which time the electrical industry had lobbied the U.S. Congress to make them mandatory safety equipment. In 1966, they were determined by Swedish chemist Dr. Soren Jensen to be an environmental contaminant,[11] and it was Dr. Jensen, according to a 1994 article in Sierra, who named them PCBs. Previously, they had simply been called "phenols" or referred to by various trade names, such as Aroclor, Kennechlor, Pyrenol, Chlorinol and others."

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3. 3. smartie 07:05 PM 5/21/10

   Has anyone tracked the association of diabetes and pancreatitis to Vietnam vets - ie., Agent Orange exposure.

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4. 4. smartie 07:12 PM 5/21/10

   Lifestyle accounts for 70%, genetics for 30% of disease, according to some experts. Lifestyle includes food, exercise, air, sunshine, stress, and environmental toxins. Too many toxins invested by man have not been scrutinized for their impact on us and our children. We need to get serious about evaluating these toxins before they are manufactured.

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5. 5. billsmith 09:34 PM 5/21/10

   @smartie
   Yes, the CDC has completed massive studies on Vietnam vets.
   http://www.cdc.gov/nceh/veterans/default1.htm
   
   Diabetes should be the least of your worries if you are exposed to high levels of dioxins.
   http://www.ncbi.nlm.nih.gov/pubmed/16281767
   
   But yes, through other studies, 2,3,7,8-Tetrachlorodibenzodioxin (TCDD) has been associated with diabetes among women and certain groups of men. (Oddly enough, it seems to treat diabetes in rats.)
   http://www.ncbi.nlm.nih.gov/pubmed/17107852
   
   I can't find a study showing relation between TCDD and pancreatic disease except for one on a possible cancer treatment. Apparently the substance is much more toxic to cancerous pancreatic and stomach cells than to healthy ones.
   http://www.ncbi.nlm.nih.gov/pubmed/12203118
   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668777/
   
   
   As for the 70/30 rule you propose, "disease" is far too vague. If I have a habit of eating cans of food potentially contaminated with botulism, no amount of good genes are going to save me from being poisoned. Likewise, "experts" is also far too vague. Are we talking about the research conclusions of epidemiologists or a casual remark by a family doctor?

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6. 6. smartie 06:57 PM 5/22/10

   bill smith - thank you so much for the links. I will read all of them.
   
   Husband spent two tours in Vietnam. Has diabetes and two bouts acute pancreatitis. Johns Hopkins endocrinologist said his pancreas is atrophied. Diabetes is in his family, pancreatitis is not and he does not have standard risk factors for pancreatitis. Will investigate the VA system for him.
   
   70% / 30% simply suggests people have significant control over their health, "Genes load the gun, but lifestyle pulls the trigger". Many believe they are victims of their genes, when they may also be victims of their family recipes, i.e., lifestyle.

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7. 7. Om_Audio in reply to billsmith 05:12 AM 5/23/10

   Hello- in response to billsmith- the article states:"... having low levels of the gamma-tocopherol form of vitamin E, found in fruits, nuts and vegetables, seemed to improve the chances an individual would not have type 2 diabetes by 7 percent. " Low levels not high.

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8. 8. Om_Audio 05:14 AM 5/23/10

   In reply to billsmith- you may have misread- "having low levels of the gamma-tocopherol form of vitamin E, found in fruits, nuts and vegetables, seemed to improve the chances an individual would not have type 2 diabetes by 7 percent. " Seems to say low levels not high.

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9. 9. Carol Hoernlein 02:02 PM 5/23/10

   Diet CERTAINLY has an influence here. I am a former food process engineer and am amazed that doctors who can link anti-bodies to glutamic acid decarboxylase to Type 1 diabetes, completely ignore the effects of excess free glutamic acid in the diet - particularly in additives like MSG that are proven to directly affect insulin levels and may possibly be the trigger that causes the body's immune system to turn on the pancreas.
   
   When you look at the effect that ingested MSG has on the pancreas it is criminal negligence that researchers are ignoring this avenue of inquiry.......

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10. 10. semoyan@hotmail.com 03:36 PM 5/24/10

    hay edicion en espa�ol.

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