Personal Genome Sequencing in Ostensibly Healthy Individuals and the PeopleSeq Consortium

Abstract

Thousands of ostensibly healthy individuals have had their exome or genome sequenced, but a much smaller number of these individuals have received any personal genomic results from that sequencing. We term those projects in which ostensibly healthy participants can receive sequencing-derived genetic findings and may also have access to their genomic data as participatory predispositional personal genome sequencing (PPGS). Here we are focused on genome sequencing applied in a pre-symptomatic context and so define PPGS to exclude diagnostic genome sequencing intended to identify the molecular cause of suspected or diagnosed genetic disease. In this report we describe the design of completed and underway PPGS projects, briefly summarize the results reported to date and introduce the PeopleSeq Consortium, a newly formed collaboration of PPGS projects designed to collect much-needed longitudinal outcome data.

The Personal Genome Project Canada: findings from whole genome sequences of the inaugural 56 participants

“…2 Information from whole genome sequencing can already identify the molecular causes of suspected heritable conditions and cancer; [2][3][4][5][6][7] however, we anticipate that genomic analysis will become a standard component of proactive health care, given its potential to identify predisposition to medically actionable conditions, explain uncharacterized disease and reveal carriers for recessive disorders and predictors of medication safety and response. 8 Interpretation of sequence data remains challenging, with unknown clinical utility and predictive value among the general population. 9 The Personal Genome Project Canada was launched in 2007, and shares the guiding principles and open consent policy of the parent project in the United States.…”

“…These volunteers do not reflect the diverse Canadian ethnicities, but we explicitly aim to expand diversity as the sample size increases, including participation from Indigenous and recent immigrant peoples. Early personal genome sequencing cohorts were suggested to be enriched for individuals with perceived risk or subtle symptoms of genetic disease; 8 although we did not enrol participants who were explicitly seeking genetic information for suspected heritable conditions, neither did we exclude participants with known health conditions ( Table 1).…”

Understanding the present and preparing for the future: Exploring the needs of diagnostic and elective genomic medicine patients

“…Outside of the clinic, public awareness of genomic tests and their potential benefits is increasing as well. A growing number of population level genomic testing initiatives have begun offering unprecedented access to personal genomic information (Linderman, Nielsen, & Green, ; Proffitt, ). These drivers are pushing genomic testing to become the “standard of care.”…”

Secondary findings: How did we get here, and where are we going?

“…Small family size additionally complicates these estimates. Prospective data are clearly needed in this area, particularly as "proactive" genetic health panels, often based on an expanded version of the ACMG SF v2.0 list (Esplin, Haverfield, Yang, Aradhya, & Nussbaum, 2018;Linderman, Nielsen, & Green, 2016;Vassy et al, 2017) and even ES/GS, become increasingly available to otherwise healthy persons in both research and commercial settings.…”