The results of the current study suggest that receiving predictive genomic risk information influences patients’ perceptions of risk and levels of worry for developing a variety of conditions, but does so in different ways and to varying degrees for different conditions. Compared with participants who received usual care, patients who received genomic information had higher initial ratings of perceived risk and levels of worry for more than half of the conditions for which they received results. However, not all differences were statistically significant or in the same direction, nor did these differences persist over time.
In contrast to concerns raised in the scientific literature9,12,29
and by organizations such as the American Society of Human Genetics,30
the American College of Medicine Genetics,31
and the Secretary’s Advisory Committee on Genetics, Health, and Society,32
we found no significant differences in levels of worry for 10 of the 12 conditions tested comparing patients who received predictive genomic risk information with those who received usual care; differences merely approached statistical significance for the remaining 2 conditions (prostate cancer and osteoarthritis). These findings are not unlike those recently reported by Bloss et al,33
who found that genome-wide testing in a non-clinical setting had no measurable impact on psychological health or behavior. Although a large percentage of patients rated themselves as being “somewhat” or “very” worried about developing conditions such as colon cancer and myocardial infarction, these percentages were similarly high for both groups of patients in our study, suggesting that the baseline level of worry for more widely known conditions is neither diminished nor enhanced by knowledge of one’s genomic risk for developing those conditions. Additionally, the relatively modest impact of predictive genomic risk information on levels of worry may be explained in part by the context in which our participants were able to discuss and interpret their risk results, namely, with the guidance of a trusted physician.
The differences in risk perception we observed between those who received predictive genomic testing and those who did not were more pronounced for diseases that are less common or are not as likely to be discussed routinely in preventive health examinations. Our results for Graves disease provide a particularly striking illustration of this point: of the patients who received predictive genomic risk information, 18% rated themselves as somewhat or very likely to develop Graves disease and 12% as somewhat or very worried about developing it, whereas none of the patients who received usual care alone had similar ratings of risk and worry. This suggests that predictive genomic testing may have a stronger impact on perceived risk of lesser-known conditions in which baseline knowledge about the disease (including its severity or likelihood) is apt to be low and information about an individual’s personalized risk of developing a rare disease is hence likely to be influential. However, because these differences disappeared with longer-term follow-up, the impact of predictive genomic testing on perceived risk of developing even lesser-known conditions appears to be temporary.
In addition, contrary to our hypothesis, we found that ratings of risk perception and worry for prostate cancer were actually lower in patients who received predictive genomic testing than in those who received usual care. The comparatively high levels of baseline risk perception and worry observed among participants who received usual care might be explained by widespread public awareness about prostate cancer and the availability of a widely used screening test (prostate-specific antigen [PSA]). This suggests that men who received a genomics-based estimate of their lifetime risk of developing prostate cancer—in addition to a negative PSA test—may have been reassured by this information and consequently lowered their ratings of perceived risk and worry. Whether altered risk perception and worry would ultimately result in fewer or less frequent requests for conventional screening tests such as PSA is an important question that our study does not address.
Several limitations of the current study deserve mention. First, the clinic population from which our sample was drawn includes primarily insured, well-educated individuals with ready access to high-quality preventive health services—characteristics that significantly limit the generalizability of our findings. Given the relatively high price of these services and the fact that they are not covered by health insurance, this is precisely the socioeconomic group being targeted by companies offering DTC predictive genomic testing products. Although our study findings are by no means conclusive in the ongoing debate regarding the impact of DTC genomic testing on patients’ perceived risk and worry, they are still salient to current policy debates. Second, given the breadth and comprehensiveness of preventive health services offered to participants in both the intervention and the control groups, effects of predictive genomic information on worry or risk perception could have been masked by what is likely, overall, a reassuring experience for patients seen in the executive health clinic. How individuals from diverse socioeconomic backgrounds might respond if they were offered such results in the context of routine primary care is unknown. For these reasons, our findings would need to be confirmed in a more representative sample of the US population before clinical practice recommendations could be made.
Finally, the largely nonsignificant results in this small study may be due in part to low statistical power or incomplete follow-up. Between 20% and 25% of participants in both arms of the study did not complete surveys at either the 1-week or 1-year follow-up period and are therefore considered “lost to follow-up.” Although unmeasured outcomes in this subsample of participants could have possibly altered our findings, the lack of significant demographic (ie, age and sex) differences between nonresponders and those who completed a survey gives us little reason to suspect that these differences would have changed our inferences.
The principal concern when translating a GWAS into preventive health care practice is establishing the accuracy of risk estimates. However, definitive data on the clinical utility of individualized genomic risk prediction—whether offered via a pure DTC approach or in the context of clinician-guided preventive care—may not be available for many years. The key ethical concern in translational genomics is managing the inevitable uncertainty that results when initial associations between genetic markers and a disease are introduced in a clinical setting before validation. Given the ambiguity and continued controversy surrounding oversight of the introduction of new genetic tests in the United States,34-36
the ultimate uncertainty about these risk estimates and their clinical importance could persist for years. Nonetheless, clinicians must now begin preparing to offer guidance for patients who purchase DTC genomics products, mixing due caution with full transparency about clinical utility.