Patients grapple with knowing their genetic screening results

Not everyone wants information about their genetic health, or all of it at once.


The field of genetics has made remarkable strides in the past few decades. More targeted therapies based on genes are becoming available, and people have more opportunities to find out their genetic makeup. Single-nucleotide polymorphisms can be analyzed, and full-exome or full-genome sequencing can be done for people with severe diseases.

But not everyone wants information about their genetic health, or all of it at once. The majority of Americans still do not know what their genome contains. Experts addressed the hows, whens and whys of managing genetic test results at the American Society of Human Genetics' annual meeting, held last November in San Francisco.

Photo by Thinkstock
Photo by Thinkstock.

Until recently, genetic tests were used primarily for Mendelian disorders. Most genomes also contain information on more common health factors, such as sensitivity to a particular medication or the likelihood of developing a particular disease, according to The Busy Physician's Guide to Genetics, Genomics, and Personalized Medicine by Kevin M. Sweet and Ron C. Michaelis.

The book's authors noted that, unlike other diagnostics that provide a positive or negative result, genetic test results could provide a probability or a spectrum of sensitivity. Despite this uncertainty, as research produces more clinically actionable results, many patients are eager to have access to their genetic information.

At the ASHG meeting, Barbara Biesecker, PhD, director of the Johns Hopkins University/National Human Genome Research Institute's Genetic Counseling Program, presented a study of patient preferences for receiving genetic test results as part of the National Human Genome Research Institute's Social and Behavioral Research Branch.

The study, which was published online by the European Journal of Human Genetics on Aug. 15, 2012, looked at a segment of participants within ClinSeq, a genome sequencing study run by the National Institutes of Health. The ClinSeq pilot is aimed at sequencing 1,500 participants to examine their genetic information in relation to health conditions such as diabetes and heart disease. All participants have an informed consent discussion with a genetic counselor prior to receiving their results.

Dr. Biesecker and her research group selected 311 of 900 participants who have so far enrolled in the ClinSeq study and asked them their preferences on receiving various types of genetic test results, as well as their perception of social norms about receiving this kind of information.

In the open response section of the survey, 294 of 311 participants preferred to learn about their results, Dr. Biesecker said.

The survey drilled down further by dividing the types of results into four categories: a gene variant that predisposes a patient to a disease that can be prevented or treated, a gene variant that predisposes a patient to a disease that cannot be prevented or treated, a gene variant that does not affect a patient's health but may be important to the health of other relatives, and uncertain gene variants that may or may not affect health.

Desire to receive results was highest for treatable diseases and diseases that revealed carrier status, with mean scores of 6.81 and 6.67, respectively, on a scale of 1 to 7, Dr. Biesecker said. Participants were less interested in gene variants for untreatable diseases and gene variants of unknown significance, with mean scores of 6.12 and 5.98.

The social norm section of the survey quantified participants' perceptions that “valued others” wanted them to have this information. Valued others could be a participant's spouse, doctor, friends, siblings or children. Participants reported that their valued others also strongly wanted them to find their genetic information in all four categories, Dr. Biesecker said.

Though the individuals in the study had an enthusiastic response to receiving their genetic results, their views are not necessarily those of the general population, she noted. The participants in the study were described as “primarily white, well educated and earning a high income.”

Other research studies suggest that all individuals will have results of clinical importance. Holly Tabor, PhD, an assistant professor of pediatrics in the Division of Bioethics at the University of Washington, described a project from the National Heart, Lung and Blood Institute (NHLBI) that looked at exomes for people of European and African descent in the NHLBI Exome Sequencing Project. Dr. Tabor's study revealed that 100% of participants had at least one known risk allele for age-related macular degeneration, for example.

“Everyone will have results,” Dr. Tabor said, but the key is deciding how to manage them. She described an innovative online approach to managing results from exome and whole genome sequencing in her presentation on the My46 project, a study on return of results run by Dr. Tabor and Michael Bamshad, MD, division chief and professor of pediatrics in the Division of Genetic Medicine at the University of Washington in Seattle. My46 allows research participants who are having their exomes sequenced as a part of research to set preferences for what information is returned to them and receive the results using the online tool.

Dr. Tabor outlined the options for receiving test results by using a transportation metaphor. The existing paradigm of clinical genetic testing is like public transportation, where you are restricted by the existing routes, stops and schedule and someone else drives—i.e., the clinician decides what test to order and what results you should receive.

In contrast, using a self-directed results management tool like My46 is like driving your own car, deciding where you want to go and when—i.e., deciding which genetic results you want and when.

“And you always have the option to leave your car at home and not know your genetic test results at all,” she added. My46 participants also have the option of contacting a genetic counselor by email, phone or videoconferencing when they set their preferences or when they receive their results.

But there are inherent risks to giving patients complete autonomy over their genetic information, said Dr. Bamshad, who spoke with ACP Hospitalist after the conference.

“Just like with symptoms, there may be information that patients do not know they need to share,” he said. “And you can't forcibly give people information.”

Also, since patients who have received complete genetic results on their own may not know what to reveal to their physicians, physicians will need to ask them for what's relevant. This becomes complicated when a genetic test done for one condition reveals unexpected secondary findings. And some of a patient's genetic information could become important in the future as a part of diagnosis or as indication of disease risk.

“[With My46] we stress the importance of the ability to change preferences over time,” said Dr. Tabor. “If your sister develops breast cancer, then you may want to know if you have risk alleles for that.” Another example, she said: Couples may want to know their carrier status for certain conditions before they have children.

The question of what to do with results becomes further complicated when the genetic information belongs to a child, said Dr. Tabor and Dr. Bamshad. Current guidelines from the American Academy of Pediatrics and the American Society of Human Genetics recommend against genetic testing of children for adult onset disorders. However, parents of children who have their exomes sequenced for other purposes will have the ability to access this information as secondary results.

Even if the parents do not want access to that information, the child may choose to view it when he or she is older, according to the experts. In children, genetic information is “a specimen you may want to go back to look at,” Dr. Bamshad said. “In fact, you may be compelled to go back and look.”