Less than two centuries after the study of genetics germinated in Mendel’s pea patch, direct-to-consumer (DTC) genome-wide disease risk profiling kits are available to anyone in America with a credit card and an internet connection. Is the era of personalized genetic risk prediction ready to bloom?
Skeptics remain unconvinced. Substantial concerns about the validity, clinical utility, and marketing claims of many commercially-available DTC test kits have been raised by scientists, physicians, the US Government Accountability Office , and the FDA . However, until regulation is imposed on such items, concerned individuals will continue to purchase test kits that purport to provide information about their risk for up to 40 polygenetic diseases. Will this genetic disease-risk information change these individuals’ health-related behavior? Will this information make them distressed or anxious?
In this week’s edition of NEJM, Drs. Cinnamon Bloss, Nicholas Schork, and Eric Topol from the Scripps Translational Science Institute (La Jolla, CA) attempt to answer these questions. They performed a prospective before-and-after analysis of a cohort of individuals undergoing direct-to-consumer genome-wide disease risk assessment with the Navigenics Health Compass, a commercially-available product of uncertain validity and clinical utility.
4891 subjects enrolled in the study by voluntarily purchasing the kit at a discounted price and completing a pre-test baseline survey; 42% of these initial subjects completed the follow-up survey approximately 3 months after testing, and were therefore included in the analysis. After adjustment for multiple demographic and study-procedure variables, there were no significant differences in the pre-specified co-primary outcomes of anxiety level, dietary fat intake, or exercise behavior from baseline to a mean follow-up period of 5.6 months. Ninety-seven percent of subjects had no clinically-significant test-related distress. Distress severity was significantly correlated with increasing average estimated lifetime risk of any condition. There was no significant increase in actual health screening or medical test utilization, but intended future use of medical testing increased significantly in a fashion that was associated with higher composite measures of all-disease risk.
What does it all mean? The authors conclude that among a group of participants who chose to purchase discounted DTC genome-wide risk profiling kits and who then completed the follow-up survey beyond 3 months, the receipt of genetic disease-risk information did not produce any short-term psychological, behavioral, or clinical effects. Importantly, very few of the ‘screening tests’ listed in the participant surveys have any demonstrable utility for the conditions assessed by the Navigenics test. Thus, following through with the ‘intended behavior change’ is likely to be of very limited value to the participants’ health. Moreover, following through with unsuitable ‘screening tests’ might imply inappropriate post-test counseling by physicians and geneticists, and may result in false positive screening test results, further investigations, more test-related distress, and wasted healthcare resources.
“This study is notable in that it is one of the first to systematically attempt to capture the responses of those who elect to take the test,” says NEJM Deputy Editor Dr Elizabeth Phimister. Does the landscape of genome-wide risk profiling have the elegant clarity of Mendel’s pea patch? Hardly. Nevertheless, it promises to provide some complex and exciting vistas in the years to come.