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Wave of the Future

obese mouse and normal mouseTwenty years ago, epidemiologists looked for simple associations between a health problem--say, obesity--and modifiable factors that impact risk, such as saturated-fat intake or cholesterol levels. Today they can explore interactions between modifiable risk factors, genetically determined predisposition, and the incidence of specific health conditions.

It's now possible to scan each study subject's genome for a half-million gene variants, natural variations in DNA that can influence why one person gets a disease while another doesn't. Correlate this data with information gleaned from study subjects and their medical records, and links emerge between variants (and their associated proteins) and disease susceptibility.

Epidemiologists at the Harvard School of Public Health are luckier than most. They can draw upon a vast bank of DNA from blood samples and cheek cells, as well as health-status data collected over two to three decades from a combined 160,000 participants in the Nurses' Health Study (NHS), Nurses' Health Study II, and the Health Professionals Follow-up Study (HPFS).

These studies are scientific goldmines, revealing associations between, for example, exercise and reduced breast cancer risk, overweight and premature death, and trans fats and heart disease. They have also disclosed ties between, say, a raised risk of certain inflammatory molecules and diabetes or, as in the case of research by HSPH's Gökhan Hotamisligil and Eric Rimm, a variant of the aP2 gene and a reduced risk of metabolic disorders.

Unfortunately, the ongoing NHS and HPFS studies are, like all U.S. research endeavors, suffering cutbacks in funding from the National Institutes of Health. "We're getting excellent scores on our renewal applications for our Health Professionals Follow-up Study funding, but we're in the middle of a funding gap, just as we were three years ago for the Nurses' Health Study," laments Walter Willett, the Fredrick John Stare Professor of Epidemiology and Nutrition and chair of the School's Department of Nutrition. He says HSPH must draw on endowment funds to help cover staff salaries until the next grant cycle.

So fruitful are these data troves, however, that Willett and colleagues plan to expand them along new lines of inquiry with help from both NIH and philanthropic supporters. For example:

Women's early-life eating habits and breast cancer. Researchers will obtain details about eating patterns in childhood and adolescence as well as input concerning their mothers' diets and relate this to chances of being diagnosed with breast malignancies.

Diet and lifestyle in pregnancy. HSPH researchers will look at linkages between diet and lifestyle variables during pregnancy in relation to the health of both mother and child. For the first time, data will be collected over the Internet--a potentially better and more cost-effective tool than paper questionnaires.

Diet and lifestyle in young men. The all-male HPFS, whose subjects were ages 40 to 75 when they signed up, will be expanded to enroll men in their 20's and 30's. No large study of younger men has yet been done, Willett says--a shortcoming given that early-life habits are proving to be powerful determinants of health later on. Again, the Internet should make efficient data collection possible, even in a time of constrained research budgets.

Ultimately, study researchers plan to ask: How do subjects' genetic blueprints also impact their disease risk? "With the genetic revolution, new opportunities for study are opening up by the month," Willett says.

"Everyone recognizes that population studies like ours are the wave of the future, but they're expensive to start up, and new ones won't yield any findings for 15 years," he continues. "NIH tried to set up a large study of pregnant women, but the cost was viewed as prohibitive--around $2 billion. Expanding our nurses' study would cost 2 or 3 percent of that."

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