"Disease genes" may not affect health
Genome-wide sequencing involves the analysis of three billion "letters" that make up human DNA, and is considered a technology that will usher in the era of disease prediction and prevention. However, sequencing the genomes of healthy people has turned out to be a very controversial issue, because no one can accurately determine the number of patients who are carriers of genetic variants that cause the risk of developing rare genetic diseases, as well as how patients themselves and their attending physicians will respond to information about these risks.
Researchers at Brigham and Women's Hospital, Harvard University and Baylor Medical College have published the results of the first randomized clinical trial that lasted 4 years, the purpose of which was to study the effect of genome-wide sequencing on primary care provided to healthy patients.
As part of the MedSeq project, 100 healthy participants and their district therapists were randomly divided into two groups, one of which underwent genome-wide sequencing, and the second acted as a control group. Each sequenced genome was analyzed for the presence of almost 5,000 gene variants associated with rare genetic conditions. The analysis involved specialists in various disciplines, including clinical and molecular genetics, primary care, ethics and jurisprudence.
According to the data obtained, 11 (22%) of the 50 participants with sequenced genomes were carriers of genetic variants identified as causing rare diseases not previously diagnosed in these people. Two of them subsequently showed symptoms of these diseases. One of these patients had a genetic variant that causes an eye disease that disrupts night vision and is known as a white-spotted fundus. This patient noted a deterioration in vision in poor lighting conditions, but did not assume that this problem could be caused by genetic causes. In the second of the patients, a genetic variant associated with variegated porphyria was identified, which served as an explanation for incomprehensible rashes and sensitivity to sunlight, from which not only the patient himself, but also his relatives suffered.
The remaining 9 patients who had predisposition genes were found to have no signs of hereditary diseases. For example, two of them had variants associated with cardiac arrhythmias, while they demonstrated good results of cardiac examinations. There is a possibility that they will develop heart problems in the future.
At the beginning of the study, the internists underwent a 6-hour training on the interpretation of a specially designed genomic testing report that fits on one page. They also had the opportunity to get advice from geneticists. After that, therapists, at their own discretion, acted with the information they received, and researchers monitored their interaction with patients for safety, as well as monitored medical, behavioral and economic results.
The authors note that they were surprised by how many practically healthy people are carriers of genetic variants associated with rare genetic diseases. In the examined sample, almost one in five turned out to be a carrier of any of the pathogenic variants. These data suggest that the potential burden of the risk of developing rare diseases in the general population may be much higher than previously thought. However, the probability that these diseases will develop in certain carriers of genetic variants is not completely clear.
The researchers also compared the two groups of participants and found that conducting genome-wide sequencing did not increase the level of anxiety in the participants of the experimental group. At the same time, they underwent more medical examinations, which increased the cost of medical care by an average of $ 350 for 6 months after receiving the sequencing results. However, the economic differences for the two groups were not statistically significant, which, apparently, is due to the smallness of the sample.
The authors note that for a number of reasons, their results should be interpreted with great caution. They also emphasize that the presence of a genetic marker in the genome does not mean that a patient will develop a certain disease.
The critical question remains whether the identification of risk markers in healthy people will be beneficial or it will push for unnecessary examinations and subsequent procedures that may cause the patient more harm than good. To get an answer to this question, it is necessary to conduct carefully planned studies of longer duration, in which more people will take part.
Article by Jason L. Vassy et al. The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial is published in the journal Annals of Internal Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on Brigham and Women's Hospital: Sequencing Healthy Patients Reveals That Many Carry Rare Genetic Disease Risks.
30.06.2017