High-throughput genomic research is characterized by a number of unique attributes, including the enormous scale of the data sets generated for a single individual, and the wide range of possible genetic results. Additionally, genomic research introduces a new paradigm in the search and delivery of genetic information, going directly from the genotype to the phenotype. These novel characteristics dictate a need to discern the motivations and expectations of research participants choosing to have their whole genome or exome sequenced.
The results of this exploratory study reveal that altruism is one of the major sources of motivation for ClinSeq participants. The motivation of altruism echoes that of other healthy research volunteers reported in the literature.7
Although financial compensation is the greatest motivation for volunteering in phase I or proof-of-principle studies, it is less valued as a motivator by healthy volunteers with higher income and education8
and older age.7
Altruism and personal health gain/benefit have been reported as particularly important motivators for volunteers of older ages.7
Among genetic studies that do not disclose individual results, there are parallel findings. Healthy volunteers have reported financial compensation as an important motivator; however, age has been inversely related to the importance of financial compensation on the decision to participate.9
Individuals affected with a specific genetic condition have reported participating in genetic studies for altruistic reasons: to help to find a gene, to help others who have or are at-risk for disease, and to help raise awareness of disease.10
In contrast, personal health gain has been reported as the greatest motivation for patients to enroll in clinical trials of cancer chemotherapy.11, 12, 13
Cancer patients may anticipate that they will derive direct benefit, even when they understand that a study is unlikely to impart any personal benefit. This is most often seen when participants' prognoses are terminal or the technology under study is viewed as ‘cutting edge'. This motivation has been described as the ‘therapeutic misconception'14, 15
and depicts the hope that research participants may experience when clinical treatments have failed to help them. In this study, the participants were healthy volunteers and patients with symptoms of coronary heart disease. Their overall health status was not as dire as that of cancer patients participating in phase-I clinical trials, thus personal health gain for ClinSeq participants is likely to carry a different meaning. In fact, the participants share more in common with early adopters of new technologies and with individuals who undergo genetic testing, than with clinical research participants who are gravely ill.
Early adaptation of new technologies typically proceeds in the face of considerable uncertainty about the potential indications, risks, and usefulness.16
Innovators and early adopters are more often information seekers and risk takers with higher formal education and higher financial status.17
They show tolerance of the uncertainties. This sophistication is reflected among the participants in this study in their expectations of whole-genome sequencing. They articulated how results may improve understanding of the cause of disease and lead to improved treatments, expectations that are consistent with the potential information that individuals could learn from having their genome sequenced.18
This understanding was further evidenced by their reasons for participating, with many hoping to learn about their risks for certain diseases, and some expecting to learn about genetic predispositions that they could possibly pass on to future offspring.
Early adopters of clinical genetic tests share characteristics with ClinSeq participants. A retrospective study of women offered BRCA1/2
testing soon after it became available, and found that uptake was associated with higher innovativeness and greater congruence between the test and their existing values. These findings are compatible with hypotheses generated by the diffusion of innovation theory.19
Similar to other studies,19, 20
most ‘early adopters' in this study were more likely to have a college degree or higher. ClinSeq participants share motivations with individuals who enroll in research in general, as well as with those who typically come forth for genetic studies and new genetic tests based on their family or personal history of disease. Individuals afflicted with a hereditary condition undergo genetic testing to provide information to family members,21, 22
gain information for self in terms of disease management,22, 23, 24
to reduce uncertainty,23
and for altruistic reasons.22
Those undergoing genetic testing because they are at risk for a specific hereditary condition cite equivalent motivations.25, 26, 27, 28, 29, 30
Interestingly, these individuals feel that in addition to providing them with the ability to guide future health-care decisions, genetic test results also aid in planning for future non-medical decisions, such as preparing advance directives and enrolling in long-term insurance.25, 26, 27, 28, 29
Overall, the findings from this study suggest that a significant proportion of early participants in whole-genome sequencing studies expect to gain information about their health risks. Taken together with the findings from an analog study,5
this suggests that participants also value having a choice about what information they can learn. When designing whole-genome sequencing studies, successful recruitment may depend on offering a choice to participants about the return of results. To do so, studies will need to anticipate providing access to clinical research support resources.31
The results of this study are limited by the characteristics of the ClinSeq cohort, which is comprised largely of individuals of higher levels of formal education and high socio-economic status. Although our findings parallel those of other early adopters, they cannot be generalized to other socio-demographic populations. The use of a multiple-choice question about participants' expectations preceding the open-ended question may have biased responses. Yet we found participants' responses replicate findings of other genetic testing and research participation studies.5
In summary, sequencing technology is predicted to continue advancing at a very rapid pace, along with further reductions in cost. In the not too distant future, whole-genome sequencing will enter clinical care. ClinSeq provides a timely opportunity to explore the motivations and expectations of participants anticipating return of high-throughput, whole-genome sequencing results in the context of translational research. Additional ClinSeq studies are ongoing to measure participants' attitudes toward intentions and decisions to learn results.