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2023-10-31 09:26:52 | onclick: | One in five healthy adults or carry pathogenic genetic variation

Researchers are divided over whether genome-wide testing should be used in clinical practice
Two new studies have shown that one in five healthy adults has a DNA mutation that may increase their risk of passing a disease.
Some scientists dream of diagnosing diseases with simple DNA scans, or at least predicting disease risk.But others say that this approach, which could soon become the basis of preventive medicine, is not worth the economic or social costs.Now, two new studies have introduced data into the debate, including the first randomized clinical trial to assess the overall genome sequence of healthy people.Both studies showed that one in five people who measured the genome sequence of healthy adults showed a risk marker for rare diseases or cancer-related genetic variations.
What this means for those people and all health-care systems associated with genetic screening remains uncertain, but some people who are interested in the study welcome the findings.Barbara Biesecker, a social and behavioral researcher at the National Human Genome Research Center in Bethesda, Maryland, said: "It's amazing that we're working on this new technology, not worrying about it behind our backs.”
The first genomic test looked at 100 healthy adults who reported family history to primary care physicians.Next, half of them were randomly assigned additional genome-wide tests, costing about $5,000 each to examine about 5 million tiny DNA sequences of 4,600 genes, known as mononucleotide mutations.
Of the 50 sequenced people, 11 had at least mutations that could cause disease, usually rare, and the researchers reported the results in an article published June 26 in the Annals of Internal Medicine (link to paper).One of the patients was extremely sensitive to the sun.Its DNA reveals a skin disease called diversity porphyria."Now, these patients know that if they were less exposed to the sun and some medical methods, they would be far less likely to get sunburns and rashes.The lead author of the study, a clinical research specialist in primary care at the Boston Department of Veterans Healthcare, said.
The team also found that each sequenced patient carried at least one recessive mutation associated with a disease — a single copy of a gene mutation that could cause disease in the presence of two copies.This knowledge can be used in fertility decisions (a couple can test to see if they carry a matching mutation) and have family members test their mutation status.
In what Vassy called "somewhat controversial results," the team examined participants' chances of developing eight multi-genic diseases, which rarely related to a single gene mutation.They edited the overall effects of these polygenic variants (70 for type II diabetes and 60 for coronary heart disease) to predict the associated risk of developing the disease.
Sixteen percent of the volunteers who reported only their family history had consulted genetic counselors or conducted follow-up laboratory tests.In the genome test group, the figure was 34%.
Some researchers have expressed concern about similar genome-wide sequencing, saying it could lead to soaring health care costs or excessive psychological damage.In addition to the initial sequencing costs (covered by the study), people who performed genomic measurements paid an average of $350 over the next six months, Vassy and colleagues reported.Contrary to concerns about emotional trauma, either the sequencing or control groups showed any anxiety or depression changes within six months of the study.
Vassy stressed that their study was small and needed further follow-up, but it still impressed Christa Martin, a health system geneticist in Danville, Pennsylvania who suggested sequencing the ACMG genome."I even think the authors underestimate their own research."Many of their patients are making healthy behavioral changes, so they are using information in a positive way," she said.”
Another article, published earlier on the preprinted text server bioRxiv, has not yet been peer-reviewed, but similar results have been achieved.Michael Snyder, director of the Center for Genomics and Personalized Medicine at Stanford University in California, and colleagues found that 12 out of 70 healthy adults were unaware of one or more DNA mutations, increasing the risk of genetic disease.
In both studies, Snyder said doctors should jump out of the 59 priority tests listed by ACMG.He argues that genome-wide sequencing should be "automatically" integrated into primary care."You may have a lot of concern, but I think that information is still very useful to doctors.However, Vassy says there is not enough evidence for insurers to reimburse healthy people for genome-wide sequencing.
"We want to fix it quickly, and now the gene has become an important cultural symbol, so we may have given it more power than it actually has."It's still a bit early to put these technologies into clinical use, " Koenig said.

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