The ClinSeq Project: Piloting large-scale genome sequencing for research in genomic medicine

ClinSeq is a pilot project to investigate the use of whole-genome sequencing as a tool for clinical research. By piloting the acquisition of large amounts of DNA sequence data from individual human subjects, we are fostering the development of hypothesis-generating approaches for performing research in genomic medicine, including the exploration of issues related to the genetic architecture of disease, implementation of genomic technology, informed consent, disclosure of genetic information, and archiving, analyzing, and displaying sequence data. In the initial phase of ClinSeq, we are enrolling roughly 1000 participants; the evaluation of each includes obtaining a detailed family and medical history, as well as a clinical evaluation. The participants are being consented broadly for research on many traits and for whole-genome sequencing. Initially, Sanger-based sequencing of 300-400 genes thought to be relevant to atherosclerosis is being performed, with the resulting data analyzed for rare, high-penetrance variants associated with specific clinical traits. The participants are also being consented to allow the contact of family members for additional studies of sequence variants to explore their potential association with specific phenotypes. Here, we present the general considerations in designing ClinSeq, preliminary results based on the generation of an initial 826 Mb of sequence data, the findings for several genes that serve as positive controls for the project, and our views about the potential implications of ClinSeq. The early experiences with ClinSeq illustrate how large-scale medical sequencing can be a practical, productive, and critical component of research in genomic medicine. Reprinted from Genome Res. 2009 Sep; 19(9): 1665-1674, with permission from Genome Research, PMID: 19602640.

• Study Weblinks:
  • ClinSeq
• Study Design:
  • Case Set
• Study Type:
  • Case Set
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 1001
• Subject Sample Telemetry Report (SSTR)

ClinSeq participants are being selected to represent the spectrum of atherosclerotic heart disease using the Framingham score (Wilson et al. 1998, PMID: 9603539) to balance accrual. The accrual target is three groups of 250 participants each who have a Framingham 10-yr coronary artery disease (CAD) risk of <5%, 5%-10%, and >10%, respectively, and an additional group of 250 participants who have a diagnosis of CAD based on a history of a myocardial infarction, coronary artery bypass graft surgery, stent placement, or other revascularization procedure. This accrual strategy was implemented so that the cohort would be enriched for detectable coronary atherosclerosis, as measured by computed tomography.

• Primary Phenotype: Atherosclerosis

• BioSample

• Principal Investigator
  • Leslie G. Biesecker, MD. National Institutes of Health, Bethesda, MD, USA.
• Funding Sources
  • National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.