Trial Information

Informed Consent for Whole Genome Sequencing: Civic Ideals and Social Norms Referenced by Early Participants

Since 2007, the cost of sequencing a diploid human genome has fallen dramatically, from
approximately $70 million to $20,000 (Illumina, 2010). As affordable sequencing platforms
become more widely available, the advancement of biomedical science will draw increasingly
on whole genome sequencing research requiring large cohorts of diverse populations (Lunshof
et al., 2009; Need & Goldstein, 2009). Key policy, ethical and legal implications of these
developments will need to be understood in order to promote the efficacy and effectiveness
of genomic research going forward.

In addition to information about well-understood regions of the genome-both sought-after and
incidental-whole genome sequencing yields results of probabilistic, uncertain, and changing
significance over indefinite periods of time. Sequence data is most useful when shared
widely among investigators in conjunction with detailed clinical information (Angrist,
2010). It may have implications for individuals and families and be of unclear clinical
significance. As such, the boundary between clinical and research testing is dissolving,
and standards for returning test results to research participants are non-existent (McGuire
& Lupski, 2010). The difficulty of acquiring informed consent' for studies involving whole
genome sequencing is therefore a topic of active debate within the biomedical research
community.

This proposed study approaches both informed consent and genomic medicine as iterative
constructs shaped by civic values and social norms. Understanding the civic and social
contexts where informed consent takes place is crucial in order to adapt it to new realities
in genomic research. An overall aim of this inquiry is to solicit feedback on the informed
consent process from some of the earliest adopters of whole genome sequencing in research.
A more specific goal is to characterize the salient personal and public references accessed
by participants around the time of the informed consent process. By highlighting trends in
and relationships between these civic values and social norms, we aim to advance the
development of an ethically and socially relevant vocabulary with which to broker terms of
use for personal sequence data.

Participants will be recruited from two NIH protocols employing whole genome sequencing for
distinct purposes. The ClinSeqTM Study is a large-scale medical sequencing project
investigating the causal role of genetics in cardiovascular disease enrolling both
symptomatic and healthy individuals. The Whole Genome Medical Sequencing for Gene Discovery
Study (WGMS) enrolls children and adults for full sequencing with the aim of discovering the
genetic etiology of rare conditions.