New gene–disease associations are reported in the literature almost weekly, but responsible use of these findings for personalized health recommendations and clinical practice may have to wait until investigators untangle gene–gene and gene–environment interactions. Meanwhile, direct-to-consumer genetic tests are on the market, raising social and behavioral questions about how the results — and limitations — of genetic testing should be communicated to the public.
"We are interested in how healthy people will react to learning about their own genetic risk profile. How well do they understand it? What will they do with this information?"Senior author Lawrence C. Brody, PhD, commented via email to Medscape Pathology & Lab Medicine. He is senior investigator at the Genome Technology Branch and chief scientific officer of the Center for Inherited Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland,.
"Our study was designed and started before the newest (and highest-profile) round of direct-to-consumer companies began offering testing. We were mainly interested in developing a framework in which to begin addressing the questions that need to be answered before genetics can be incorporated into routine healthcare," said Dr. Brody.
The article notes that unequal access to genetic assessments might increase current disparities in healthcare. In addition, inadequate understanding of underlying genetic processes could cause unnecessary worry or, conversely, a false sense of security. The track record of patients following health guidelines for weight, smoking, and exercise is also unimpressive, leading some to question whether genetic "risk" information will produce any health benefits.
A relatively small increase in risk is associated with most gene–disease associations. "I think many in the field of human genetics, and the general public, have yet to come to grips with the true nature of these genetic risk factors," noted Dr. Brody. "They are more akin to mild environmental risk factors (ie, a slightly elevated cholesterol level or a few extra pounds) than they are to any of the familiar Mendelian conditions."
The article anticipates a need for multidisciplinary teams consisting of "social scientists, clinicians, epidemiologists, biologists, psychologists, ethicists and health service researchers" to deal with the social and behavioral aspects of susceptibility testing.
"I think the broad range of expertise needed to address issues of multiplex testing is out there. The difficulties are that scientists from different disciplines do not speak the same language and do not always value the same scientific approaches," lead author Colleen M. McBride, PhD, chief and senior investigator, Social and Behavioral Research Branch, National Human Genome Research Institute, told Medscape Pathology & Lab Medicine via email.
"Expanded opportunities for the types of transdisciplinary collaboration that we have constructed with the Multiplex Initiative are needed. To be a model for this type of collaboration was part of the goal of the Multiplex Initiative," Dr. McBride added.
The Multiplex Initiative will study a sample of adults to determine who is interested in genetic risk testing, responses to the test results, and whether they can interpret results correctly. The study also investigates the psychological and social differences between individuals who choose genetic testing and those who reject it.
Medscape Pathology & Lab Medicine also received email comments from Lloyd Michener, MD, professor and chair, Department of Community and Family Medicine, and director, Duke Center for Community Research, Duke University Medical Center, Durham, North Carolina.
"Our own experience with the local community is that people differ in what information they want how and when; rarely is the issue unidimensional. And the trust in the group offering the testing/counseling is at least as important as the test itself. One critique of the multiplex project is that it may not adequately assess the degree of trust people have (or do not have) in [the sponsoring institutions]," observed Dr. Michener. He is not an author of the commentary.
The Multiplex Initiative tests for 15 genes associated with susceptibility to 8 common diseases: colorectal cancer, coronary heart disease, hypercholesterolemia, hypertension, lung cancer, malignant melanoma, osteoporosis, and type 2 diabetes. It was estimated that most individuals tested would carry 4 to 10 risk variants of the genes, indicating a higher-than-average risk for developing a given disease.
Recruitment to the initiative began early in 2007. Of more than 4000 individuals approached, more than 2000 completed baseline surveys, more than 500 have accessed the study Web site, and 300 have opted for testing. Recruitment is still underway, with a target of 500 individuals who choose genetic testing. The study is not yet ready to report outcomes.
Dr. McBride explained: "We expect that the findings from this early phase research could generate a good deal of other research questions and hypotheses and, as such, iteratively influence the research to follow. For example, if we find that...the worried well [are] disproportionately seeking out multiplex testing, and it is associated with unnecessary follow-up tests and healthcare costs, a next round of research might aim to learn more about how physicians or the healthcare system can redirect these patients to be better consumers of health information."
The initiative will also identify areas of confusion or misunderstanding of genetic information to study in future research.
"The Multiplex Initiative has caused quite a stir in the field, because of its innovation...colleagues always speculate about how it will work, how it will be used, etc," Deborah J. Bowen, PhD, from the Social and Behavioral Sciences Department, Boston University, Massachusetts, told Medscape Pathology & Lab Medicine via email. She is not an author of the commentary.
"I am hoping that the initiative will have more influence when its results are released and the rest of us can learn from and build on those results. It's an exciting opportunity to see innovation happen right in front of us," Dr. Bowen concluded.
Dr. Brody, Dr. McBride, Dr. Michener, and Dr. Bowen have disclosed no relevant financial relationships.
Nat Genet. 2008;40(8):939–942.