A recent article discusses a landmark program that involves DNA screening of healthy individuals to identify genetic variants associated with disease.
The development of technologies that allow for the rapid and affordable sequencing of entire human genomes has accelerated medical research and is expected to make actionable genetic information available to health service providers as well as patients and healthy individuals. A landmark effort that was first initiated in 2007 and is still underway is attempting to sequence the protein-coding DNA sequences (or exomes) of approximately half a million healthy human volunteers in counties across central, south-central, and northeast Pennsylvania.1
Pioneering DNA Screening Program
This pioneering DNA screening program, which is run by the Danville-based Geisinger Health System in partnership with the New York-based Regeneron Pharmaceuticals, is expected to integrate genetic information into existing healthcare programs to assess disease risk and help implement strategies to prevent disease onset.
The program, as recently described in Science, enrolled its first volunteers in the year 2007 as part of the MyCode Community Health Initiative. Subsequently, in the year 2013, the program was expanded in its scope and christened the GenomeFIRST initiative. The program has enrolled more than 166,000 Pennsylvanians and sequenced the exomes of more than 92,400 people so far. It informs screened individuals in the case that mutations are detected in 76 genes that are known to be associated with the disease. These 76 genes are linked with 27 disease conditions, which include cancer and cardiovascular disease. Mutations associated with conditions such as Alzheimer’s disease are not disclosed, as well-defined treatment options are not available for these conditions. Of the people screened, 417 people have been identified with 420 mutations involving 36 different genes.
People enrolled in the screening program can elect to be informed of the genetic results that are pertinent to their health. Once potentially deleterious mutations are detected, the program coordinator informs the individual concerned who can then contact the coordinator for more information and subsequently set up meetings with his/her primary care physician or genetic counsellor for further discussions. Patients are also encouraged to discuss the results with their family and complete a family history, which can help determine how diseases run through families. Apart from improving the health outcomes for patients with potential disease-causing mutations, this pioneering program hopes to develop systems that would enable primary health care providers to integrate the genetic information and devise follow-ups with relatives who could also be at risk for disease.
Cost-Effectiveness and Scalability
Key questions remain about the cost-effectiveness and scalability of such programs. While the cost of whole exome sequencing is currently below 1000 dollars, additional screening for the disease and follow-up tests add to the cost. A study, which analyzed the impact of DNA sequencing in healthy adults on primary care and health outcomes, found that physicians ordered too many tests after DNA sequencing, which substantially increased the overall costs.2 Also, in cases where the patient fails to go through follow up after screening and being identified as high risk, the initial DNA screening would amount to wasteful expenditure. These raise questions about the scalability of DNA screening programs. The results of GenomeFIRST may well decide if similar programs are implemented in other parts of the globe.
Written by Usha B. Nair, Ph.D.
1) Trivedi, BP. Is health care ready for routine DNA screening? A massive new trial will find out. http://www.sciencemag.org/news/2017/10/health-care-ready-routine-dna-screening-massive-new-trial-will-find-out. Published: Oct 26, 2017. Accessed: November 5, 2017.
2) Vassy JL, Christensen KD, Schonman EF, Blout CL, Robinson JO, Krier JB, Diamond PM, Lebo M, Machini K, Azzariti DR, Dukhovny D, Bates DW, MacRae CA, Murray MF, Rehm HL, McGuire AL, Green RC; MedSeq Project. The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial. Ann Intern Med. 2017 Jun 27. doi: 10.7326/M17-0188. [Epub ahead of print] PubMed PMID: 28654958.