Researchers disagree on whether genome-wide testing should now be applied clinically.
Two new studies have shown that one in five healthy adults has a DNA mutation that may increase their risk of passing on the disease.
Some scientists dream of diagnosing diseases with simple DNA scans, or at least predicting disease risk.But others say the 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 to this debate, one of which is the first randomized clinical trial to evaluate the overall genome sequence of healthy people.Both studies showed that one in five people who measured genome sequences in healthy adults showed risk markers for rare diseases or genetic variants associated with cancer.
What this means for those people and for all health care systems associated with genetic screening remains uncertain, but some who are concerned about the study welcome the findings.Barbara Biesecker, a social and behavioral researcher at the National Center for Human Genome Research in Bethesda, Maryland, said: "It's remarkable that we're working on implementing this new technology, rather than worrying about it behind our backs.”
The first genomic testing study looked at 100 healthy adults who reported family genetic history to primary care physicians.Next, half of them were randomly assigned to another whole-genome test, a process that costs about $5,000 per person to examine about 5 million tiny DNA sequence changes, or single nucleotide variations, in 4,600 genes.
Of the 50 people sequenced, 11 had at least one mutation that could lead to disease, often rare disease, the researchers reported in an article published June 26 in the Annals of Internal Medicine.One of the patients was extremely sensitive to the sun.Its DNA revealed a skin condition called diversity porphyria."Now, these patients know that if they had less exposure to the sun and some medical treatments, they would have a much lower chance of getting sunburns and rashes."The study's lead author, a primary care clinical research specialist in the Boston Department of Veterans Affairs' health care system, said.
The team also found that each sequenced patient carried at least one recessive mutation associated with one disease — a single copy of the gene mutation that could cause the disease in the presence of two copies.This knowledge can be used in fertility decisions (a couple can be tested to see if they carry a matching mutation) and have family members test their mutation carrying status.
In what Vassy called "some controversial results," the team examined participants' odds of developing eight polygenic diseases, a condition rarely associated with individual genetic variants.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 in patients.
Sixteen percent of the volunteers who reported only their family history had consulted a genetic counselor or conducted follow-up laboratory tests.In the genomic testing group, this figure was 34%.
Some researchers have expressed concern about similar whole genome sequencing, arguing that it could send medical costs soaring or cause excessive psychological harm.In addition to the initial sequencing costs (covered by the study), people who took the genome measurements paid an average of another $350 over the next six months, Vassy and colleagues reported.But contrary to concerns about emotional trauma, either the sequencing or control groups showed any change in anxiety or depression within six months of the study.
Vassy emphasized that their study was small and needed further follow-up, but the study still impressed health system geneticist Christa Martin, of Danville, Pennsylvania, who had made recommendations for ACMG genome sequencing."I think the authors underestimated their research."A lot of their patients are generating healthy behavioral changes, so they're using the information in a positive way."”
Another article, published earlier in the preprint text server bioRxiv, has not yet been peer reviewed, but has produced similar results.Using whole exome sequencing to examine protein coding regions of the genome, 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 variants.
In both studies, Snyder said doctors should jump out of the 59 priority gene ranges listed by the ACMG.He believes whole genome sequencing should be "automated" into primary care."You may have a lot of concerns, but I think this information is still very useful for doctors."However, Vassy says there is not enough evidence to allow insurers to reimburse healthy people for genome-wide sequencing.
"We wanted to fix it quickly, and now genes have become an important cultural symbol, so we may have given it more power than it actually can.""It's still a bit too early for these technologies to be applied clinically," Koenig said.