Wednesday, July 11, 2012
Detailed knowledge about your genetic makeup—the interplay between genetic variants and other genetic variants, or between genetic variants and environmental risk factors—may only change your estimated disease prediction risk for three common diseases by a few percentage points, which is typically not enough to make a difference in prevention or treatment plans, say researchers. The study by Harvard School of Public Health (HSPH) researchers is the first to revisit claims in previous research that including such information in risk models would eventually help doctors either prevent or treat diseases. "While identifying a synergistic effect between even a single genetic variant and another risk factor is known to be extremely challenging and requires studies with a very large number of individuals, the benefit of such discovery for risk prediction purpose might be very limited," said lead author Hugues Aschard, research fellow in the Department of Epidemiology. Scientists have long hoped that using genetic information gleaned from the Human Genome Project and other genetic research could improve disease risk prediction enough to help aid in prevention and treatment. Others have been skeptical that such "personalized medicine" will be of clinical benefit. Still others have argued that there will be benefits in the future, but that current risk prediction algorithms underperform because they don''t allow for potential synergistic effects—the interplay of multiple genetic risk markers and environmental factors—instead focusing only on individual genetic markers. Aschard and his co-authors, including senior author Peter Kraft, HSPH associate professor of epidemiology, examined whether disease risk prediction would improve for breast cancer, type 2 diabetes, and rheumatoid arthritis if they included the effect of synergy in their statistical models. But they found no significant effect by doing so. "Statistical models of synergy among genetic markers are not 'game changers' in terms of risk prediction in the general population," said Aschard. The researchers conducted a simulation study by generating a broad range of possible statistical interactions among common environmental exposures and common genetic risk markers related to each of the three diseases. Then they estimated whether such interactions would significantly boost disease prediction risk when compared with models that didn''t include these interactions since, to date, using individual genetic markers in such predictions has provided only modest improvements. For breast cancer, the researchers considered 15 common genetic variations associated with disease risk and environmental factors such as age of first menstruation, age at first birth, and number of close relatives who developed breast cancer.