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New genetic contributors to diseases are discovered daily, and an increasing number of companies offer to scan individuals’ genomes for linkages between genes and disease. On June 10 members of the public and experts gathered at the Center’s Genetic Perspectives on Policy Seminar (GenePOPS), "The Molecular Full Monty: Personal Genomes, Personal Health," to discuss the growth in whole-genome tests, the extent to which consumers understand their results and what they do with them, and the power of the tests to predict an individual’s risk of disease.
Many companies now offer genetic tests directly to the consumer, without physician involvement. Center director and event moderator Kathy Hudson told the audience that the situation raises many questions, including:
(1) How much scientific evidence is available to support the linkages identified by the genome services?
(2) Is it useful to know if you have a slightly increased or decreased risk of a common complex disease?
(3) Do the results change people’s behavior and in what ways?
(4) Where will the personal genomics trend go from here?
Hudson introduced four speakers: George Church, professor of genetics and director of the Center for Computational Genetics at Harvard Medical School; Henry “Hank” Greely, the Deane F. and Kate Edelman Johnson Professor of Law at Stanford University; Colleen McBride, chief and senior investigator of the Social and Behavioral Research Branch at the National Human Genome Research Institute; and Robert Green, professor of neurology, genetics and epidemiology at Boston University’s Schools of Medicine and Public Health.
What is the science behind genetic testing?
Church explained that ways of analyzing an individual’s genome range in thoroughness from chip-based services that only analyze 0.02 percent of the genome, to sequencing 98 percent of the genome. He described techniques that have brought the price of sequencing down by a factor of a thousand from what it was at the time the first human genome was sequenced. To further decrease the price, Church is involved in the Personal Genome Project, which aims to “bring down [to] less than 1,000 dollars not just getting a genome sequenced, but also getting something that is highly informative.” He concluded by telling the audience about developments in 2007 that enabled scientists to analyze gene expression in multiple tissues by reprogramming an individual’s skin cells, and stressed the importance of interactions between genes and environment in determining disease risk and drug response.
What are the ethical and legal issues?
“It’s important to pay attention to what kind of test, what kind of company you’re looking at…there’s a lot of variation,” Greely said as he began his presentation. That said, he enumerated four major concerns about direct-to-consumer genome testing:
• Companies failing to warn customers about privacy risks, especially if a company goes bankrupt or is subpoenaed, and the risk of discovering information that you did not want to know, such as that you are not related to the people that you thought you were.
• The gap between the predictive power of genetic testing results and consumer expectations of that power. The commonly available genome scanning services omit some genes known to be strong predictors of disease. Additionally, these tests only look at genes, and do not take into account other potentially powerful information such as lifestyle and environment.
• The lack of context. Most genome-scanning companies do not have or require a medical intermediary. People may misinterpret their results and make an erroneous health decisions as a result.
• Genetic testing of children. Greely strongly believes that kids should not undergo genetic tests or sequencing unless the results would be important to their current health.
What will people do with their genetic test results?
There are very few studies that involve conducting genetic testing for common complex diseases, giving feedback to individuals, and then evaluating the impact of the data on their health habits, McBride stressed at the outset of her remarks. “In terms of the data that we have around the question of whether [genetic] data can influence behavior change we really have a lot of optimism…but very little data to support most of those assertions,” McBride said. The smoking cessation studies she is involved in have not shown any evidence of lifestyle changes based on genetic test results. On the other hand, they have not shown that people gain a false sense of security about their health habits based on the test results, as some have feared. To address the lack of data, McBride is involved in the Multiplex Initiative, designed to answer three questions:
• Who might be interested in genetic testing for modest risk of common complex diseases?
• Will individuals who seek testing be able to understand the results?
• How might the test results influence individuals seeking other risk information, such as family disease history and behavioral risks?
The study approached 4,000 individuals to see if they were interested in genetic testing for 15 different genes that play a role in eight common conditions – type 2 diabetes, coronary heart disease, high blood cholesterol, high blood pressure, osteoporosis, lung cancer, colorectal cancer, and malignant melanoma. The tests look for common variants of these genes that slightly alter an individual’s risk of disease. Eleven percent went through with the testing. “When you aggregate that to the population level, that’s actually a large number of individuals who might be approaching a physician with test results in a system that’s really not prepared to handle it,” McBride said. She also showed survey results demonstrating that participants appreciate that both genetic and environmental factors contribute to disease risk.
Revealing all?
Green, a researcher who has had his own genome scanned, also discussed how people respond to the results of genetic tests. According to Green, a mutation in the APOE gene is “probably the most robust risk marker for Alzheimer’s disease. It’s been known for a long time, but no one’s used it for predictive purposes because of all the ethical issues.” Therefore, Green and his colleagues decided to explore its clinical validity, whether people wanted to know if they carried the risk marker, and, if so, what they did with the information. Through a series of randomized clinical trials, Green discovered that many people want to know their APOE allele, and that, when participants are screened and educated on the subject beforehand and have access to genetic counselors, the psychological impact of the results is minimal. Additionally, he found that participants generally understand and recall the information given to them about the test, that people would change their health habits and take out life insurance if a result came back showing a genetic predisposition for Alzheimer disease, and that people’s pre-existing perceptions of their Alzheimer risk are resistant to change.
Green concluded his presentation by sharing his Navigenics and 23andMe genetic screening results. He pointed out that the two companies returned contradictory results for his risk of heart disease. Navigenics’ results indicated a higher than average risk, and his 23andMe results showed a slightly lower than average risk. Considering that he has no family history of heart disease, does not smoke, exercises, and does not have cholesterol problems, Green inferred that his risk was low. Subsequently, however, he suffered from three-vessel disease. “If anybody was at a genetic risk for heart disease, it was me because there were no environmental factors… but in the one instance, at least in my life, where this could have alerted me, it did not,” Green said.
“The currently available genetic information on health is of limited or, in some cases, no medical value, and it may actually falsely frighten or falsely reassure consumers,” Green continued. “While I truly believe that these companies are ethical and committed to improving people’s health, I believe that market forces may push them in the direction of exaggerating the benefits of the product. Genetic information coupled with health information, however, could have a public health benefit.”
Discussion
Hudson brought up the difference in the positions of the American Society of Human Genetics, which holds some genetic tests may be appropriate for sale directly to consumers without the involvement of a health care provider, and the American College of Medical Genetics, which takes the position that all genetic tests require the counsel of a health care provider. She questioned the panelists about whether physicians need to be involved in the genetic testing process. All panel members agreed that the need for involvement falls on a continuum because of the varying gravity and complexity of test results. Greely said that he would rather err on the side of safety and see trained professionals available. McBride pointed out that individuals will likely bring health-related direct-to-consumer results to their physicians, who will need to be prepared to respond.
Stephanie Devaney of the Children’s National Medical Center and Scott Douglas of the Department of Health and Human Services asked questions about Green’s Alzheimer disease study. They wondered if participants who had a genetic link to Alzheimer disease were changing their behavior because they were experiencing more anxiety than they reported, and if participants’ preexisting risk perceptions were resistant to change because the participants had some prior experience with someone who had Alzheimer disease. Green agreed that these were strong possibilities. He also said that purchasing supplements because of a genetic risk of Alzheimer disease is “scary because it highlights the way that this information could be used [by] the nutraceutical industry.” In “unscrupulous hands” companies could market vitamins and supplements based on consumers’ genetic profiles, he said.
Greg Lennon of SNPedia, an online collection of information from scientific publications about single nucleotide polymorphisms, commented that the Web site “grows by three to five single nucleotide polymorphisms per day that are newly reported.” However, a person having his or her genome read is getting a report at a single period of time, and reported risks could change over time as new discoveries are made.
Lennon also commented that genetic testing and sequencing is an international phenomenon, and questioned the panel on what is happening internationally. The panelists were in consensus that this is a very new issue, and governments are trying to get a grip on the science and clinical utility in order to regulate personal genome services. Greely pointed out that, “It’s not just different national jurisdictions; different states have different regulations that have some significant effect with respect to the ordering of tests, the role of doctors, and the doctor-patient relationship.”
Scott Boyle, a AAAS fellow at the Department of Health and Human Services, questioned the panelists on what methods they thought would be useful to increase consumer understanding of risk and the connections between genes and disease. McBride responded that educating consumers about the risks and limitations of genetic tests is the biggest thing that can be done, and it would enable people to be critical of the tests. Green thought it inevitable that people will become better educated about genetic testing, and that legitimate consumer genetics companies “are going to be major positive forces in doing that.” Greely had a list of ideas. “I would like to see more good journalism on this, pointing out the limitations on some of the tests. I’d like to see something on a Web site, maybe in an NHGRI [National Humane Genome Research Institute] Web site, spelling out in very clear language what some of the limitations on these probabilistic tests are. And I continue to think there’s an important role for professionals as intermediaries, whether it’s geneticists, primary care physicians, genetic counselors, or others, to help people make sense of this information. Over time, the ability to make sense of it will diffuse throughout the population. But the faster we can make that diffusion happen, the fewer tragedies or even misunderstandings and mistakes there will be.”
John Compton of GeneDX, a company that conducts genetic testing for rare hereditary diseases, asked the final question: Who monitors the accuracy of the data and analysis of genetic tests?
A video of the event will be posted on the Center Web site within a few weeks. – Katherine Groff
Transcript of the event
