Friday, January 11, 2008

NEJM Article on "Letting the Genome out of the Bottle"

This week's New England Journal of Medicine has an interesting Perspectives article by David Hunter et. al. entitled "Letting the Genome out of the Bottle — Will We Get Our Wish". Here is a sample:

It may happen soon. A patient, perhaps one you have known for years, who is overweight and does not exercise regularly, shows up in your office with an analysis of his whole genome at multiple single-nucleotide polymorphisms (SNPs). His children, who were concerned about his health, spent $1,000 to give him the analysis as a holiday gift. The test report states that his genomic profile is consistent with an increased risk of both heart disease and diabetes, and because the company that performed the analysis stated that the test was "not a clinical service to be used as the basis for making medical decisions," he is in the office for some "medical direction." What should you do?

This year has seen a dizzying number of genomewide association studies demonstrating associations between novel gene variants or chromosomal loci and common diseases and phenotypes. These studies rely on microarrays that can assess 300,000 or more SNPs in each DNA sample; researchers use these microarrays to examine interpersonal differences in inherited genetic variability and to compare the prevalence of gene variants among patients who have a given disease with that among controls. Such studies have identified associations with many gene variants that were not previously suspected to be related to the phenotypes under consideration. The new technologies involved have been a boon to researchers who needed unbiased clues as to the causation of diseases that may be used to develop new therapeutic and preventive interventions. The test undergone by the patient described above is one of the products of this new knowledge.

....So what advice should a physician offer patients? For the patient who appears with a genome map and printouts of risk estimates in hand, a general statement about the poor sensitivity and positive predictive value of such results is appropriate, but a detailed consumer report may be beyond most physicians' skill sets. For the patient asking whether these services provide information that is useful for disease avoidance, the prudent answer is "Not now — ask again in a few years." More information is needed on the clinical utility of this information in the light of existing disease-specific opportunities for prevention or early detection and the potential value that genomic profiles can add to that of simpler tools, such as the family health history. Finally, given the risk of commercial exploitation, if patients are determined to proceed, perhaps because they are simply curious, are genetic hobbyists, or are "early adopters" of new technology, it would make sense to encourage them to enroll in formal scientific studies.

Now that the genome is out of the bottle, how will our wish for better health be granted? Just as the emergence of a commercial entity (Celera) with ambitions to sequence the human genome spurred public projects to accelerate their efforts, perhaps the emergence of commercial personalized genomic services will galvanize efforts to plan and conduct the necessary translational research5 for the rational integration of genomic information into medical training and practice. Until the genome can be put to useful work, the children of the man described above would have been better off spending their money on a gym membership or a personal trainer so that their father could follow a diet and exercise regimen that we know will decrease his risk of heart disease and diabetes.