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									New Scientist
Want to know your disease risk? Check your exposome

21 December 2010 by Jessica Hamzelou
Magazine issue 2792.

WHEN it comes to health, which is more important, nature or nurture? You may well
think your genes are a more important predictor of health and ill health. Not so fast. In
fact, it transpires that our everyday environment outweighs our genetics, big time, when it
comes to measuring our risk of disease. The genome is out - welcome the exposome.

"The exposome represents everything a person is exposed to in the environment, that's
not in the genes," says Stephen Rappaport, environmental health scientist at the
University of California, Berkeley. That includes stress, diet, lifestyle choices,
recreational and medicinal drug use and infections, to name a few. "The big difference is
that the exposome changes throughout life as our bodies, diets and lifestyles change," he
says.

While our understanding of the human genome has been growing at an exponential rate
over the last decade, it is not as helpful as we hoped in predicting diseases. "Genes only
contribute 10 per cent of the overall disease burden," says Rappaport.

"Knowing genetic risk factors can prove absolutely useless," says Jeremy Nicholson at
Imperial College London. He points to work by Nina Paynter at the Brigham and
Women's Hospital in Boston, who investigated the effects of 101 genetic markers
implicated in heart disease. After following over 19,000 women for 12 years, she found
these markers were not able to predict anything about the incidence of heart disease in
this group (The Journal of the American Medical Association DOI:
10.1001/jama.2010.119).

On the other hand, the impact of environmental influences is still largely a mystery.
"There's an imbalance between our ability to investigate the genome and the
environment," says Chris Wild, director of the International Agency for Research on
Cancer, who came up with the idea of the exposome.

In reality, most diseases are probably caused by a combination of the two, which is where
the exposome comes in. "The idea is to have a comprehensive analysis of a person's full
exposure history," says Wild. He hopes a better understanding of exposures will shed a
brighter light on disease risk factors.

There are likely to be critical periods of exposure in development. For example, the time
from birth to 3 years of age is thought to be particularly important. "We know that this is
the time when brain connections are made, and that if you are obese by this age, you'll
have problems as an adult," says Nicholson.
In theory, a blood or urine sample taken from an individual could provide a snapshot of
what that person has been exposed to. But how do you work out what fingerprints
chemicals might leave in the body?

The task is not as formidable as it sounds. For a start, researchers could make use of
swathes of biobank information that has already been collected. "There has been a huge
international funding effort in adult cohorts like the UK Biobank already," says Wild. "If
we improved analysis, we could apply it to these groups."

Several teams are also working towards developing wearable devices to measure personal
exposure to chemicals in the environment, for example (see "Bugging your biosphere").

"We can put chemicals in categories," says Rappaport. "We could start by prioritising
toxic chemicals, and look for markers of these toxins in the blood, while hormones and
metals can be measured directly."

Rappaport is looking at albumin, a common protein in the blood that transports toxins to
the liver where they are processed and broken down. He wants to know how it reacts with
a range of chemicals, and is measuring the products. "You can get a fingerprint - a
display of all the products an individual has been exposed to."

By combining this information with an enhanced understanding of how exposure affects
health, the exposome could help better predict a person's true disease risk. And we
shouldn't have to wait long - Rappaport reckons we can reap the benefits within a
generation.

To this end, the US National Institutes of Health has set up an exposure biology
programme. "We're looking for interactions between genes and exposure to work out an
individual's risk of disease," says David Balshaw, who manages the programme. "It
would allow you to tailor the therapeutic response to that person's risk."

An understanding of this interaction, reflected in a person's metabolic profile, might also
help predict how they will respond to a drug. Nicholson has been looking for clues in
metabolite profiles of urine samples.

Last year, his research group used these profiles to predict how individuals would
metabolise paracetamol. "It turned out that gut microbes were very important," says
Nicholson. "We've shown that the pre-dose urinary metabolite profile could predict the
metabolism of analgesic drugs, and therefore predict drug toxicity." The findings suggest
that metabolic profiles of exposure could help doctors tailor therapies and enable them to
prescribe personalised medicines.

Justin Stebbing at Imperial College London has already shown that metabolic profiles of
women with breast cancer can predict who will respond to certain therapies. It is early
days, but the initial findings look promising.
"We're reaching the point where we're capable of assessing the exposome," says Balshaw.
With the implications for understanding disease causes and risks, and a real prospect of
developing personalised medicine, the exposome is showing more promise than the
genome already, he adds.

Bugging your biosphere
How does air pollution or stress leave a trace in the blood? The US National Institutes of
Health in Bethesda, Maryland, is trying to find out.

One group funded by the NIH and led by Nongjian Tao at Arizona State University's
Biodesign Institute in Tempre is developing wearable wireless sensors to monitor an
individual's exposure to environmental pollutants.

The group have come up with a wearable sensor - roughly the size of a cellphone - that
detects levels of pollutants from car exhaust. The sensor then converts this information
into an electrical signal, which is transmitted via Bluetooth to the wearer's cellphone,
which then displays what chemicals you are exposed to.

Tao's team started by creating software for Windows phones, but they are working on
apps that could be used on any smartphone. In theory, anyone could pop on a sensor and
download an app to receive real-time information on exposure to environmental
pollutants.

At the same time, smartphones monitoring your location can combine the level of
pollution with an exact time and place. Tao presented his sensor at the Circuits and
Systems for Medical and Environmental Applications Workshop in Yukatán Mexico last
week.

"We're now moving prototypes into human studies, and progressing those prototypes into
products," says David Balshaw of the NIH.

Earlier this year, Tao's group tried out the sensor on individuals taking a stroll around Los
Angeles, California. They were able to measure how exposure to pollutants changed as
each person wandered near busy roads and petrol stations.


From issue 2792 of New Scientist magazine, page 6-7.

								
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