A Model for Genome-First Care: Returning Secondary Genomic Findings to Participants and Their Healthcare Providers in a Large Research Cohort

American Journal of Human Genetics

Volumn 103, Issue 3, 2018, Pages 328-337

  Schwartz, Marci L B ^a   McCormick, Cara Zayac ^a   Lazzeri, Amanda L ^a   Lindbuchler, D'Andra M ^a,c   Hallquist, Miranda L G ^a   Manickam, Kandamurugu ^a,d   Buchanan, Adam H ^a   Rahm, Alanna Kulchak ^a   Giovanni, Monica A ^a   Frisbie, Lauren ^a   Flansburg, Carroll N ^a   Davis, F Daniel ^a   Sturm, Amy C ^a   Nicastro, Christine ^a   Lebo, Matthew S ^b   Mason Suares, Heather ^b   Mahanta, Lisa Marie ^b   Carey, David J ^a   Williams, Janet L ^a   Williams, Marc S ^a   Ledbetter, David H ^a   Faucett, W Andrew ^a   Murray, Michael F ^a,e   more..

^a Geisinger Center for Health   (United States)

^b Laboratory for Molecular Medicine   (United States)

^c Wilkes Barre Area Career and Technical Center   (United States)

^d NATIONWIDE CHILDREN S HOSPITAL   (United States)

^e YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

care delivery; genetics; genomics; incidental findings; learning healthcare system; population screening; public health; research results; secondary findings; whole exome sequencing

Indexed keywords

ADULT; ARTICLE; CLINICAL EVALUATION; COHORT ANALYSIS; ELECTRONIC HEALTH RECORD; FEMALE; FOLLOW UP; GENOME; GENOMICS; HEALTH CARE PERSONNEL; HEALTH CARE SYSTEM; HUMAN; HUMAN EXPERIMENT; INCIDENTAL FINDING; LEARNING; MAJOR CLINICAL STUDY; MALE; MASS SCREENING; RELATIVE; WHOLE EXOME SEQUENCING; DNA SEQUENCE; GENETICS; HUMAN GENOME; PROCEDURES;

COHORT STUDIES; ELECTRONIC HEALTH RECORDS; GENOME, HUMAN; GENOMICS; HEALTH PERSONNEL; HUMANS; SEQUENCE ANALYSIS, DNA;

EID: 85056388580     PISSN: 00029297     EISSN: 15376605     Source Type: Journal    
DOI: 10.1016/j.ajhg.2018.07.009     Document Type: Article

References (24)

1. Wetterstrand, K.A. (2016). DNA Sequencing Costs: Data from the NHGRI Genome Sequencing Program (GSP) 2016 [4/28/2017]. Available from: www.genome.gov/sequencingcostsdata.
2. Green, R.C., Berg, J.S., Berry, G.T., Biesecker, L.G., Dimmock, D.P., Evans, J.P., Grody, W.W., Hegde, M.R., Kalia, S., Korf, B.R., et al. Exploring concordance and discordance for return of incidental findings from clinical sequencing. Genet. Med. 14 (2012), 405–410.
3. Green, R.C., Berg, J.S., Grody, W.W., Kalia, S.S., Korf, B.R., Martin, C.L., McGuire, A.L., Nussbaum, R.L., O'Daniel, J.M., Ormond, K.E., et al., American College of Medical Genetics and Genomics. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet. Med. 15 (2013), 565–574.
4. Kalia, S.S., Adelman, K., Bale, S.J., Chung, W.K., Eng, C., Evans, J.P., Herman, G.E., Hufnagel, S.B., Klein, T.E., Korf, B.R., et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet. Med. 19 (2017), 249–255.
5. Carey, D.J., Fetterolf, S.N., Davis, F.D., Faucett, W.A., Kirchner, H.L., Mirshahi, U., Murray, M.F., Smelser, D.T., Gerhard, G.S., Ledbetter, D.H., The Geisinger MyCode community health initiative: an electronic health record-linked biobank for precision medicine research. Genet. Med. 18 (2016), 906–913.
6. Dewey, F.E., Murray, M.F., Overton, J.D., Habegger, L., Leader, J.B., Fetterolf, S.N., O'Dushlaine, C., Van Hout, C.V., Staples, J., Gonzaga-Jauregui, C., et al. Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study. Science, 354, 2016, 354.
7. Faucett, W.A., Davis, F.D., How Geisinger made the case for an institutional duty to return genomic results to biobank participants. Appl. Transl. Genomics 8 (2016), 33–35.
8. Amendola, L.M., Dorschner, M.O., Robertson, P.D., Salama, J.S., Hart, R., Shirts, B.H., Murray, M.L., Tokita, M.J., Gallego, C.J., Kim, D.S., et al. Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 25 (2015), 305–315.
9. Yang, Y., Muzny, D.M., Xia, F., Niu, Z., Person, R., Ding, Y., Ward, P., Braxton, A., Wang, M., Buhay, C., et al. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 312 (2014), 1870–1879.
10. Retterer, K., Juusola, J., Cho, M.T., Vitazka, P., Millan, F., Gibellini, F., Vertino-Bell, A., Smaoui, N., Neidich, J., Monaghan, K.G., et al. Clinical application of whole-exome sequencing across clinical indications. Genet. Med. 18 (2016), 696–704.
11. Williams, M.S., Buchanan, A.H., Davis, F.D., Faucett, W.A., Hallquist, M.L.G., Leader, J.B., Martin, C.L., McCormick, C.Z., Meyer, M.N., Murray, M.F., et al. Patient-centered precision health in a learning health care system: Geisinger's genomic medicine experience. Health Aff. (Millwood) 37 (2018), 757–764.
12. Psek, W.A., Stametz, R.A., Bailey-Davis, L.D., Davis, D., Darer, J., Faucett, W.A., Henninger, D.L., Sellers, D.C., Gerrity, G., Operationalizing the learning health care system in an integrated delivery system. EGEMS (Wash. DC), 3, 2015, 1122.
13. IOM, Genomics-Enabled Learning Health Care Systems: Gathering and Using Genomic Information to Improve Patient Care and Research: Workshop Summary. 2015, The National Academies Press, Washington, DC.
14. Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W.W., Hegde, M., Lyon, E., Spector, E., et al., ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17 (2015), 405–424.
15. Duzkale, H., Shen, J., McLaughlin, H., Alfares, A., Kelly, M.A., Pugh, T.J., Funke, B.H., Rehm, H.L., Lebo, M.S., A systematic approach to assessing the clinical significance of genetic variants. Clin. Genet. 84 (2013), 453–463.
16. Stuckey, H., Williams, J.L., Fan, A.L., Rahm, A.K., Green, J., Feldman, L., Bonhag, M., Zallen, D.T., Segal, M.M., Williams, M.S., Enhancing genomic laboratory reports from the patients’ view: A qualitative analysis. Am. J. Med. Genet. A. 167A (2015), 2238–2243.
17. Williams, J.L., Rahm, A.K., Stuckey, H., Green, J., Feldman, L., Zallen, D.T., Bonhag, M., Segal, M.M., Fan, A.L., Williams, M.S., Enhancing genomic laboratory reports: A qualitative analysis of provider review. Am. J. Med. Genet. A. 170A (2016), 1134–1141.
18. Murray, M.F., Your DNA is not your diagnosis: getting diagnoses right following secondary genomic findings. Genet. Med. 18 (2016), 765–767.
19. Abul-Husn, N.S., Manickam, K., Jones, L.K., Wright, E.A., Hartzel, D.N., Gonzaga-Jauregui, C., O'Dushlaine, C., Leader, J.B., Lester Kirchner, H., Lindbuchler, D.M., et al. Genetic identification of familial hypercholesterolemia within a single U.S. health care system. Science, 354, 2016, 354.
20. Haggerty, C.M., James, C.A., Calkins, H., Tichnell, C., Leader, J.B., Hartzel, D.N., Nevius, C.D., Pendergrass, S.A., Person, T.N., Schwartz, M., et al. Electronic health record phenotype in subjects with genetic variants associated with arrhythmogenic right ventricular cardiomyopathy: a study of 30,716 subjects with exome sequencing. Genet. Med. 19 (2017), 1245–1252.
21. Schoenbaum, S.C., Keys to a high-performance health system for the United States. Healthc. Financ. Manage. 60 (2006), 60–64 66.
22. Coorevits, P., Sundgren, M., Klein, G.O., Bahr, A., Claerhout, B., Daniel, C., Dugas, M., Dupont, D., Schmidt, A., Singleton, P., et al. Electronic health records: new opportunities for clinical research. J. Intern. Med. 274 (2013), 547–560.
23. Gottesman, O., Kuivaniemi, H., Tromp, G., Faucett, W.A., Li, R., Manolio, T.A., Sanderson, S.C., Kannry, J., Zinberg, R., Basford, M.A., et al., eMERGE Network. The Electronic Medical Records and Genomics (eMERGE) Network: past, present, and future. Genet. Med. 15 (2013), 761–771.
24. Chambers, D.A., Feero, W.G., Khoury, M.J., Convergence of implementation science, precision medicine, and the learning health care system: a new model for biomedical research. JAMA 315 (2016), 1941–1942.