Informed Consent for Whole Genome Sequencing: Ideals and Norms Referenced by Early Participants
Condition: Coronary Artery Disease; Proteus Syndrome; Coffin - Sins Syndrome; Familial Isolated Hyperparathyroidism; Dubouitz Syndrome
MeSH terms: Proteus Syndrome; Coronary Artery Disease; Hyperparathyroidism; Syndrome
Study type: Observational

Summary: 
      Since 2007, the cost of sequencing a diploid human genome has fallen dramatically, from
      approximately $70 million to $20,000. 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. 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.

      An overall aim of this project is to obtain feedback on the informed consent process from
      some of the earliest particpants in studies using whole genome sequencing. 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 participants views
      about study participation around the time of the initial informed consent process, we aim to
      advance the development of an ethically and socially relevant vocabulary with which to
      negotiate future terms of use for personal sequence data in genomic research.

      Participants will be asked to complete a one-time, semi-structured telephone interview
      lasting approximately 45 minutes in the period 2-8 weeks following their initial informed
      consent session at the NIH. They will be recruited from two NIH protocols employing whole
      genome sequencing for distinct purposes. They 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.
    

Detailed description: 
      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.

      <TAB>

      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.
    

Time perspective: Prospective
Keywords: Civic Ideals/Social Norms; Genetic Counseling; Genetic Disorders; Genetic Testing; Whole Genome Sequencing