The gene-environment enigma & personalized medicine

From the December 3, 2010 news item

Personalized medicine centers on being able to predict the risk of disease or response to a drug based on a person’s genetic makeup. But a study by scientists at Washington University School of Medicine in St. Louis suggests that, for most common diseases, genes alone only tell part of the story.

That’s because the environment interacts with DNA in ways that are difficult to predict, even in simple organisms like single-celled yeast, their research shows.

“The effects of a person’s genes – and, therefore, their risk of disease – are greatly influenced by their environment,” says senior author Barak Cohen, PhD, a geneticist at Washington University School of Medicine. “So, if personalized medicine is going to work, we need to find a way to measure a human’s environment.”

The research is available online in PLoS Genetics….

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The new research raises many questions: what is a human’s environment and how can it be measured? Is the environment a person lived in during childhood important or the environment he lives in now?

Cohen suspects that any environment that matters is likely to leave a measurable molecular signature. For example, eating a lot of fatty foods raises triglycerides; smoking raises nicotine levels; and eating high-fat, high-sugar foods raises blood sugar levels, which increases the risk of diabetes. The key, he says, is to figure out what are good metabolic readouts of the environment and factor those into statistical models that assess genetic susceptibility to disease or response to medication.

“Measuring the environment becomes crucial when we try to understand how it interacts with genetics,” Cohen says. “Having a particular genetic variant may not have much of an effect but combined with a person’s environment, it may have a huge effect.”

Cohen says he’s not hopeless when it comes to personalized medicine. As scientists conduct ever-larger studies to identify rare and common variants underlying diseases such as cancer, diabetes and schizophrenia, they will be more likely to uncover variants that have larger effects on disease. Even then, however, a person’s environment will be important, he adds.