With a scan through a sample of genomes from several individuals, researchers can tease out links among genetic variations and particular diseases. These genome-wide association studies have clarified some of the genes involved in predisposing people for  rheumatoid arthritis, bipolar disorder, Crohn's disease, diabetes and other disorders, paving the way for new study and better treatments.

For many complex diseases, however, genetics tell only part of the story. Environmental factors, such as diet and chemical exposure, have become increasingly obvious players in determining a person's risk of various diseases. But these environmental exposures have long been regarded as too nuanced and variable to measure with the same specificity as genetics.

A team of researchers at Stanford University is hoping to change that. In a study, published online May 20 in the journal PLoS ONE, they describe a new, environmental-based risk factor screening for type 2 diabetes, a technique they have dubbed environmental-wide association study (or EWAS, after GWAS, which stands for genome-wide association study). It promises to uncover new environmental links for this disease and others.

"Everyone's been focused on the genetic causes of the disease," says Atul Butte, an assistant professor of biomedical informatics and pediatrics at Stanford. But, he notes, lately "people are dissatisfied with the little amount of risk we can explain with genetics."

Genetic flags for type 2 diabetes, from which 23.6 million people in the U.S. suffer, have failed to explain away much of an individual's apparent risk. And even though macro lifestyle factors, such as high sugar intake and little exercise, have been shown to increase a person's risk for diabetes, Butte and his colleagues were not satisfied. "Are we that sure nothing else in the environment is playing a role in diabetes?" he asks.

According to their new analysis of 266 environmental variables and the presence of type 2 diabetes in thousands of individuals who participated in a national health survey, Butte and his team were able to confirm suspected links, including PCBs (polychlorinated biphenyls, which are now banned in the U.S. but can still be found in old capacitors, fiberglass and adhesives), and also uncover new ones, such as a pesticide product and a common form of vitamin E.

Bioinformatics for the environment
The environmental components people come into contact with throughout their lives are basically endless, so assessing an individual's total history of exposure might seem impossible. But with data from the National Health and Nutrition Examination Survey (administered by the U.S. Centers for Disease Control and Prevention), Butte and his colleagues were able to get solid information on environmental factors (measured from blood and urine samples and logged in databases) and individuals' health, disease diagnoses and fasting blood sugar levels (an indicator that can show the presence of diabetes).

Though the studied list of environmental factors is by no means exhaustive, the chemical variables can be analyzed along the same lines as selected single-nucleotide polymorphisms (SNPs) that geneticists run on a genetic chip. "They can't put every variant on there," Butte says of genomic researchers. But when a scan does pick up a particular SNP, it might represent dozens of others that were not specifically being tested. So rather than providing a comprehensive list, both genetics and the EWAS model can detect a signal that indicates "we should be looking at that entire category" of chemicals or SNPs, he says.

The project came about as an idea from a Stanford graduate student, Chirag Patel, the lead author on the study, who approached Butte wanting to find a way "to use bioinformatics for the environment," Butte explains.

Patel created a specialized computer program to assess the relevant information gathered from the CDC's health survey databases. After controlling for age, sex, body mass index, ethnicity and socioeconomic status, the group found that those with high levels of PCBs had a 15 percent chance of having type 2 diabetes, a correlation that had been shown in previous studies. They also found that high levels of beta-carotene seemed to have a protective effect, reducing risk of having diabetes by about 9 percent (another link that had been seen in other studies, though had not been proven in clinical trials).

The big surprises came from a chemical previously found in pesticides and a common form of vitamin E—levels of which seemed to influence the chances that an individual would have diabetes. Heptachlor epoxide is derived from a pesticide that was banned in the U.S. in the 1980s. It is still found in soil and water supplies and can turn up in food and be passed along in breast milk. High levels of it seemed to increase type 2 diabetes risk to about 7 percent. And 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.

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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