Skip to main content
Advanced searchCitation search
Skip main navigation
 
Original Research
27 June 2017

The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial

Authors: Jason L. Vassy, MD, MPH, SM, Kurt D. Christensen, PhD, MPH, Erica F. Schonman, MPH, Carrie L. Blout, MS, CGC, Jill O. Robinson, MA, Joel B. Krier, MD, Pamela M. Diamond, PhD, … Show All … , Matthew Lebo, PhD, Kalotina Machini, PhD, Danielle R. Azzariti, MS, CGC, Dmitry Dukhovny, MD, MPH, David W. Bates, MD, MSc, Calum A. MacRae, MD, PhD, Michael F. Murray, MD, Heidi L. Rehm, PhD, Amy L. McGuire, JD, PhD, and Robert C. Green, MD, MPH, for the MedSeq Project Author, Article, & Disclosure Information
Publication: Annals of Internal Medicine
Volume 167, Number 3
https://doi.org/10.7326/M17-0188
Get Access

Submit a Comment

Contributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.
Cancel

Abstract

Background:

Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value.

Objective:

To describe the effect on clinical care and outcomes of adding WGS to standardized family history assessment in primary care.

Design:

Pilot randomized trial. (ClinicalTrials.gov: NCT01736566)

Setting:

Academic primary care practices.

Participants:

9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years.

Intervention:

Patients were randomly assigned to receive a family history report alone (FH group) or in combination with an interpreted WGS report (FH + WGS group), which included monogenic disease risk (MDR) results (associated with Mendelian disorders), carrier variants, pharmacogenomic associations, and polygenic risk estimates for cardiometabolic traits. Each patient met with his or her PCP to discuss the report.

Measurements:

Clinical outcomes and health care use through 6 months were obtained from medical records and audio-recorded discussions between PCPs and patients. Patients' health behavior changes were surveyed 6 months after receiving results. A panel of clinician-geneticists rated the appropriateness of how PCPs managed MDR results.

Results:

Mean age was 55 years; 58% of patients were female. Eleven FH + WGS patients (22% [95% CI, 12% to 36%]) had new MDR results. Only 2 (4% [CI, 0.01% to 15%]) had evidence of the phenotypes predicted by an MDR result (fundus albipunctatus due to RDH5 and variegate porphyria due to PPOX). Primary care physicians recommended new clinical actions for 16% (CI, 8% to 30%) of FH patients and 34% (CI, 22% to 49%) of FH + WGS patients. Thirty percent (CI, 17% to 45%) and 41% (CI, 27% to 56%) of FH and FH + WGS patients, respectively, reported making a health behavior change after 6 months. Geneticists rated PCP management of 8 MDR results (73% [CI, 39% to 99%]) as appropriate and 2 results (18% [CI, 3% to 52%]) as inappropriate.

Limitation:

Limited sample size and ancestral and socioeconomic diversity.

Conclusion:

Adding WGS to primary care reveals new molecular findings of uncertain clinical utility. Nongeneticist providers may be able to manage WGS results appropriately, but WGS may prompt additional clinical actions of unclear value.

Primary Funding Source:

National Institutes of Health.

Get full access to this article

View all available purchase options and get full access to this article.

Get Access

Supplemental Material

Supplement. Supplementary Material

References

1.
Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, et al. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA. 2014;312:1870-9. [PMID: 25326635]  doi: 10.1001/jama.2014.14601
Crossref
PubMed
Google Scholar
2.
Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing. N Engl J Med. 2014;370:2418-25. [PMID: 24941179]  doi: 10.1056/NEJMra1312543
Crossref
PubMed
Google Scholar
3.
Beaudet AL. Using fetal cells for prenatal diagnosis: History and recent progress. Am J Med Genet C Semin Med Genet. 2016;172:123-7. [PMID: 27133782]  doi: 10.1002/ajmg.c.31487
Crossref
PubMed
Google Scholar
4.
Cuckle H, Benn P, Pergament E. Cell-free DNA screening for fetal aneuploidy as a clinical service. Clin Biochem. 2015;48:932-41. [PMID: 25732593]  doi: 10.1016/j.clinbiochem.2015.02.011
Crossref
PubMed
Google Scholar
5.
Gagan J, Van Allen EM. Next-generation sequencing to guide cancer therapy. Genome Med. 2015;7:80. [PMID: 26221189]  doi: 10.1186/s13073-015-0203-x
Crossref
PubMed
Google Scholar
6.
Relling MV, Evans WE. Pharmacogenomics in the clinic. Nature. 2015;526:343-50. [PMID: 26469045]  doi: 10.1038/nature15817
Crossref
PubMed
Google Scholar
7.
Selkirk CG, Weissman SM, Anderson A, Hulick PJ. Physicians' preparedness for integration of genomic and pharmacogenetic testing into practice within a major healthcare system. Genet Test Mol Biomarkers. 2013;17:219-25. [PMID: 23390885]  doi: 10.1089/gtmb.2012.0165
Crossref
PubMed
Google Scholar
8.
Feero WG, Manolio TA, Khoury MJ. Translational research is a key to nongeneticist physicians' genomics education. Genet Med. 2014;16:871-3. [PMID: 24875299]  doi: 10.1038/gim.2014.67
Crossref
PubMed
Google Scholar
9.
Christensen KD, Vassy JL, Jamal L, Lehmann LS, Slashinski MJ, Perry DL, et al; MedSeq Project Team. Are physicians prepared for whole genome sequencing? a qualitative analysis. Clin Genet. 2016;89:228-34. [PMID: 26080898]  doi: 10.1111/cge.12626
Crossref
PubMed
Google Scholar
10.
Kohane IS, Hsing M, Kong SW. Taxonomizing, sizing, and overcoming the incidentalome. Genet Med. 2012;14:399-404. [PMID: 22323072]  doi: 10.1038/gim.2011.68
Crossref
PubMed
Google Scholar
11.
Trinidad SB, Fullerton SM, Burke W. Looking for trouble and finding it. Am J Bioeth. 2015;15:15-7. [PMID: 26147255]  doi: 10.1080/15265161.2015.1039731
Crossref
PubMed
Google Scholar
12.
Vassy JL, Lautenbach DM, McLaughlin HM, Kong SW, Christensen KD, Krier J, et al; MedSeq Project. The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine. Trials. 2014;15:85. [PMID: 24645908]  doi: 10.1186/1745-6215-15-85
Crossref
PubMed
Google Scholar
13.
Robinson JO, Carroll TM, Feuerman LZ, Perry DL, Hoffman-Andrews L, Walsh RC, et al; MedSeq Project Team. Participants and study decliners' perspectives about the risks of participating in a clinical trial of whole genome sequencing. J Empir Res Hum Res Ethics. 2016;11:21-30. [PMID: 26928896]  doi: 10.1177/1556264615624078
Crossref
PubMed
Google Scholar
14.
Office of the Surgeon General. My Family Health Portrait: A Tool From the Surgeon General. Accessed at https://familyhistory.hhs.gov/FHH/html/index.html on 19 April 2017.
Google Scholar
15.
McLaughlin HM, Ceyhan-Birsoy O, Christensen KD, Kohane IS, Krier J, Lane WJ, et al; MedSeq Project. A systematic approach to the reporting of medically relevant findings from whole genome sequencing. BMC Med Genet. 2014;15:134. [PMID: 25714468]  doi: 10.1186/s12881-014-0134-1
Crossref
PubMed
Google Scholar
16.
Vassy JL, McLaughlin HM, McLaughlin HL, MacRae CA, Seidman CE, Lautenbach D, et al. A one-page summary report of genome sequencing for the healthy adult. Public Health Genomics. 2015;18:123-9. [PMID: 25612602]  doi: 10.1159/000370102
Crossref
PubMed
Google Scholar
17.
Kong SW, Lee IH, Leshchiner I, Krier J, Kraft P, Rehm HL, et al; MedSeq Project. Summarizing polygenic risks for complex diseases in a clinical whole-genome report. Genet Med. 2015;17:536-44. [PMID: 25341114]  doi: 10.1038/gim.2014.143
Crossref
PubMed
Google Scholar
18.
Snaith RP, Zigmond AS. The hospital anxiety and depression scale [Letter]. Br Med J (Clin Res Ed). 1986;292:344. [PMID: 3080166]
Crossref
PubMed
Google Scholar
19.
DeSalvo KB, Fan VS, McDonell MB, Fihn SD. Predicting mortality and healthcare utilization with a single question. Health Serv Res. 2005;40:1234-46. [PMID: 16033502]
Crossref
PubMed
Google Scholar
20.
Chao S, Roberts JS, Marteau TM, Silliman R, Cupples LA, Green RC. Health behavior changes after genetic risk assessment for Alzheimer disease: The REVEAL Study. Alzheimer Dis Assoc Disord. 2008;22:94-7. [PMID: 18317253]  doi: 10.1097/WAD.0b013e31815a9dcc
Crossref
PubMed
Google Scholar
21.
Fitch K, Bernstein SJ, Aguilar MD, Burnand B, LaCalle JR, Lazaro P, et al. The RAND/UCLA Appropriateness Method User's Manual. Santa Monica, CA: RAND Corporation; 2001.
Google Scholar
22.
Nalichowski R, Keogh D, Chueh HC, Murphy SN. Calculating the benefits of a Research Patient Data Repository. AMIA Annu Symp Proc. 2006:1044. [PMID: 17238663]
PubMed
Google Scholar
23.
Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43:1130-9. [PMID: 16224307]
Crossref
PubMed
Google Scholar
24.
Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, 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. 2017;19:249-255. [PMID: 27854360]  doi: 10.1038/gim.2016.190
Crossref
PubMed
Google Scholar
25.
Manolio TA, Chisholm RL, Ozenberger B, Roden DM, Williams MS, Wilson R, et al. Implementing genomic medicine in the clinic: the future is here. Genet Med. 2013;15:258-67. [PMID: 23306799]  doi: 10.1038/gim.2012.157
Crossref
PubMed
Google Scholar
26.
Prince AE, Berg JS, Evans JP, Jonas DE, Henderson G. Genomic screening of the general adult population: key concepts for assessing net benefit with systematic evidence reviews. Genet Med. 2015;17:441-3. [PMID: 25232850]  doi: 10.1038/gim.2014.129
Crossref
PubMed
Google Scholar
27.
Feero WG, Wicklund C, Veenstra DL. The economics of genomic medicine: insights from the IOM Roundtable on Translating Genomic-Based Research for Health. JAMA. 2013;309:1235-6. [PMID: 23532238]  doi: 10.1001/jama.2013.113
Crossref
PubMed
Google Scholar
28.
Khoury MJ, Berg A, Coates R, Evans J, Teutsch SM, Bradley LA. The evidence dilemma in genomic medicine. Health Aff (Millwood). 2008;27:1600-11. [PMID: 18997217]  doi: 10.1377/hlthaff.27.6.1600
Crossref
PubMed
Google Scholar
29.
Grosse SD. Economic analyses of genetic tests in personalized medicine: clinical utility first, then cost utility. Genet Med. 2014;16:225-7. [PMID: 24232411]  doi: 10.1038/gim.2013.158
Crossref
PubMed
Google Scholar
30.
Bell CJ, Dinwiddie DL, Miller NA, Hateley SL, Ganusova EE, Mudge J, et al. Carrier testing for severe childhood recessive diseases by next-generation sequencing. Sci Transl Med. 2011;3:65ra4. [PMID: 21228398]  doi: 10.1126/scitranslmed.3001756
Crossref
PubMed
Google Scholar
31.
Cassa CA, Tong MY, Jordan DM. Large numbers of genetic variants considered to be pathogenic are common in asymptomatic individuals. Hum Mutat. 2013;34:1216-20. [PMID: 23818451]  doi: 10.1002/humu.22375
Crossref
PubMed
Google Scholar
32.
Olfson E, Cottrell CE, Davidson NO, Gurnett CA, Heusel JW, Stitziel NO, et al. Identification of medically actionable secondary findings in the 1000 Genomes. PLoS One. 2015;10:e0135193. [PMID: 26332594]  doi: 10.1371/journal.pone.0135193
Crossref
PubMed
Google Scholar
33.
Salgado D, Bellgard MI, Desvignes JP, Béroud C. How to identify pathogenic mutations among all those variations: variant annotation and filtration in the genome sequencing era. Hum Mutat. 2016;37:1272-1282. [PMID: 27599893]  doi: 10.1002/humu.23110
Crossref
PubMed
Google Scholar
34.
Dorschner MO, Amendola LM, Turner EH, Robertson PD, Shirts BH, Gallego CJ, et al; National Heart, Lung, and Blood Institute Grand Opportunity Exome Sequencing Project. Actionable, pathogenic incidental findings in 1,000 participants' exomes. Am J Hum Genet. 2013;93:631-40. [PMID: 24055113]  doi: 10.1016/j.ajhg.2013.08.006
Crossref
PubMed
Google Scholar
35.
Harrison SM, Riggs ER, Maglott DR, Lee JM, Azzariti DR, Niehaus A, et al. Using ClinVar as a resource to support variant interpretation. Curr Protoc Hum Genet. 2016;89:8. [PMID: 27037489]  doi: 10.1002/0471142905.hg0816s89
Crossref
PubMed
Google Scholar
36.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, 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. 2015;17:405-24. [PMID: 25741868]  doi: 10.1038/gim.2015.30
Crossref
PubMed
Google Scholar
37.
Berg JS, Foreman AK, O'Daniel JM, Booker JK, Boshe L, Carey T, et al. A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing. Genet Med. 2016;18:467-75. [PMID: 26270767]  doi: 10.1038/gim.2015.104
Crossref
PubMed
Google Scholar
38.
Hunter JE, Irving SA, Biesecker LG, Buchanan A, Jensen B, Lee K, et al. A standardized, evidence-based protocol to assess clinical actionability of genetic disorders associated with genomic variation. Genet Med. 2016;18:1258-1268. [PMID: 27124788]  doi: 10.1038/gim.2016.40
Crossref
PubMed
Google Scholar
39.
Green RC, Goddard KA, Jarvik GP, Amendola LM, Appelbaum PS, Berg JS, et al; CSER Consortium. Clinical Sequencing Exploratory Research consortium: accelerating evidence-based practice of genomic medicine. Am J Hum Genet. 2016;98:1051-66. [PMID: 27181682]  doi: 10.1016/j.ajhg.2016.04.011
Crossref
PubMed
Google Scholar
40.
ACMG Board of Directors. Clinical utility of genetic and genomic services: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2015;17:505-7. [PMID: 25764213]  doi: 10.1038/gim.2015.41
Crossref
PubMed
Google Scholar
41.
Grosse SD, Rogowski WH, Ross LF, Cornel MC, Dondorp WJ, Khoury MJ. Population screening for genetic disorders in the 21st century: evidence, economics, and ethics. Public Health Genomics. 2010;13:106-15. [PMID: 19556749]  doi: 10.1159/000226594
Crossref
PubMed
Google Scholar

Comments

0 Comments
Sign In to Submit A Comment

Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 167 • Number 3 • 1 August 2017
Pages: 159 - 169

History

Published online: 27 June 2017
Published in issue: 1 August 2017

Keywords

  1. Behavior
  2. Disclosure
  3. Electronic medical records
  4. Genetics
  5. Health care
  6. Health surveys
  7. Multidrug resistance
  8. Pathogens
  9. Pharmacogenomics
  10. Primary care physicians

Copyright

© 2017 American College of Physicians.

Authors

Affiliations

Jason L. Vassy, MD, MPH, SM
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Kurt D. Christensen, PhD, MPH
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Erica F. Schonman, MPH
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Carrie L. Blout, MS, CGC
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Jill O. Robinson, MA
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Joel B. Krier, MD
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Pamela M. Diamond, PhD
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Matthew Lebo, PhD
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Kalotina Machini, PhD
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Danielle R. Azzariti, MS, CGC
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Dmitry Dukhovny, MD, MPH
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
David W. Bates, MD, MSc
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Calum A. MacRae, MD, PhD
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Michael F. Murray, MD
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Heidi L. Rehm, PhD
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Amy L. McGuire, JD, PhD
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
Robert C. Green, MD, MPH,
From VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, and Partners HealthCare Personalized Medicine, Boston, Massachusetts; Baylor College of Medicine and UTHealth School of Public Health, Houston, Texas; Oregon Health & Science University, Portland, Oregon; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and Geisinger Health System, Danville, Pennsylvania.
View all articles by this author
for the MedSeq Project
View all articles by this author
Disclaimer: The contents do not necessarily represent the views of the U.S. Department of Veterans Affairs (VA), the U.S. government, Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health (NIH).
Acknowledgment: The authors thank 5AM Solutions (Rockville, Maryland) for their help in customizing the workflow of the My Family Health Portrait Web tool for this study. The authors thank the patient participants, physician participants, and genetics panelists of the MedSeq Project. Dr. Vassy affirms that he has listed everyone who contributed significantly to this work.
Financial Support: By grant U01-HG006500 from the National Human Genome Research Institute of the NIH. Dr. Vassy is an employee of the VA Boston Healthcare System and received support from NIH grant KL2-TR001100 and Career Development Award IK2-CX001262 from the VA Clinical Sciences Research and Development Service. Drs. Green and Rehm are also supported by NIH grants U19-HD077671, U01-HG008685, and U41-HG006834 and by funding from the Broad Institute of MIT and Harvard. Dr. Christensen is supported by NIH grant K01-HG009173. Dr. MacRae's work in this area is supported by NIH grant U01-HG007690 and by the Burroughs Wellcome Fund. This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and National Center for Advancing Translational Sciences, NIH grant UL1-TR001102) and financial contributions from Harvard University and its affiliated academic health care centers.
Disclosures: Ms. Blout reports grants from the NIH during the conduct of the study. Dr. Lebo reports grants from the National Human Genome Research Institute during the conduct of the study. Dr. Machini reports grants from the NIH during the conduct of the study. Ms. Azzariti reports grant support from the National Human Genome Research Institute of the NIH during the conduct of the study. Dr. Dukhovny reports consulting for Vermont Oxford Network, Gerson Lehrman Group, and ClearView Healthcare Partners and being faculty for Vermont Oxford Network outside the submitted work. Dr. Bates reports grants from EarlySense; personal fees from S.E.A. Medical Systems, EarlySense, QPID Health, Center for Digital Innovation (Negev), Enelgy, Valera Health, Intensix, and MDClone; and equity from S.E.A. Medical Systems, QPID Health, Enelgy, Valera Health, Intensix, and MDClone outside the submitted work. In addition, Dr. Bates has a patent for Medicalis with royalties paid to Brigham and Women's Hospital. Dr. Bates chaired the FDASIA workgroup, which has advised the U.S. Food and Drug Administration, the Federal Communications Commission, and the Office of the National Coordinator on the regulation of health care information technology including mobile technology, and also served as a member of the Health Information Technology Policy Committee. Dr. MacRae reports grants from the NIH during the conduct of the study. In addition, Dr. MacRae has a patent for gene testing in cardiomyopathies with royalties paid to Partners HealthCare. Dr. Murray reports personal fees from InVitae and Merck and grants from Regeneron outside the submitted work. Dr. Rehm reports grants from the NIH during the conduct of the study, payment for advisory board services from Genome Medical outside the submitted work, and employment at Partners HealthCare Laboratory for Molecular Medicine and The Broad Institute of MIT and Harvard (fee-based services) outside the submitted work. Dr. McGuire reports grants from MedSeq during the conduct of the study. Dr. McGuire is a consultant for Human Longevity outside the submitted work. Dr. Green reports personal fees from Illumina, Invitae, Helix, GenePeeks, Veritas, and Ohana and is a cofounder with equity in Genome Medical. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0188.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement: Study protocol, statistical code, and data set: Available from Dr. Vassy (e-mail, [email protected]).
Corresponding Author: Jason L. Vassy, MD, MPH, SM, VA Boston Healthcare System, 150 South Huntington Avenue, 152-G, Boston, MA 02115; e-mail, [email protected].
Current Author Addresses: Dr. Vassy: 150 South Huntington Avenue, 152-G, Boston, MA 02130.
Drs. Christensen, Krier, and Green; Ms. Schonman; and Ms. Blout: 41 Avenue Louis Pasteur, Suite 301, Boston, MA 02115.
Ms. Robinson and Dr. McGuire: 1 Baylor Plaza, Suite 310D, Houston, TX 77030.
Dr. Diamond: 7000 Fannin, UCT Suite 2614, Houston, TX 77030.
Drs. Lebo, Machini, and Rehm and Ms. Azzariti: 65 Landsdowne Street, Suite 350, Cambridge, MA 02139.
Dr. Dukhovny: 707 SW Gaines Street, Mail Code-CDRC-P, Portland, OR 97239.
Dr. Bates: 1620 Tremont Street, 3rd Floor, BC3-2M, Boston, MA 02120.
Dr. MacRae: Building for Transformative Medicine, 7016F, 60 Fenwood Road, Boston, MA 02115.
Dr. Murray: 190 Welles Street, Suite 128, Forty Fort, PA 18704.
Author Contributions: Conception and design: J.L. Vassy, K.D. Christensen, E.F. Schonman, J.B. Krier, D.W. Bates, M.F. Murray, H.L. Rehm, A.L. McGuire, R.C. Green.
Analysis and interpretation of the data: J.L. Vassy, K.D. Christensen, E.F. Schonman, J.O. Robinson, J.B. Krier, P.M. Diamond, M. Lebo, K. Machini, D.R. Azzariti, D. Dukhovny, D.W. Bates, C.A. MacRae, M.F. Murray, H.L. Rehm.
Drafting of the article: J.L. Vassy, K.D. Christensen, E.F. Schonman, J.O. Robinson, H.L. Rehm, R.C. Green.
Critical revision of the article for important intellectual content: J.L. Vassy, K.D. Christensen, E.F. Schonman, C.L. Blout, J.O. Robinson, J.B. Krier, K. Machini, D. Dukhovny, D.W. Bates, C.A. MacRae, M.F. Murray, H.L. Rehm, A.L. McGuire, R.C. Green.
Final approval of the article: J.L. Vassy, K.D. Christensen, E.F. Schonman, C.L. Blout, J.O. Robinson, J.B. Krier, P.M. Diamond, M. Lebo, K. Machini, D.R. Azzariti, D. Dukhovny, D.W. Bates, C.A. MacRae, M.F. Murray, H.L. Rehm, A.L. McGuire, R.C. Green.
Provision of study materials or patients: J.L. Vassy, C.L. Blout, C.A. MacRae, M.F. Murray.
Statistical expertise: J.L. Vassy, K.D. Christensen, P.M. Diamond.
Obtaining of funding: M.F. Murray, H.L. Rehm, A.L. McGuire, R.C. Green.
Administrative, technical, or logistic support: J.L. Vassy, E.F. Schonman, C.L. Blout, J.O. Robinson, J.B. Krier, D.R. Azzariti, H.L. Rehm.
Collection and assembly of data: J.L. Vassy, K.D. Christensen, E.F. Schonman, C.L. Blout, J.O. Robinson, J.B. Krier, M. Lebo, D.R. Azzariti, C.A. MacRae, M.F. Murray, H.L. Rehm, A.L. McGuire.
This article was published at Annals.org on 27 June 2017.
* For members of the MedSeq Project, see the Appendix.

Metrics & Citations

Metrics

Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. For an editable text file, please select Medlars format which will download as a .txt file. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format




Tips for downloading citations

Download article citation data for:
Jason L. Vassy, Kurt D. Christensen, Erica F. Schonman, et al; for the 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;167:159-169. [Epub 27 June 2017]. doi:10.7326/M17-0188

View More

Login Options:
Purchase

You will be redirected to acponline.org to sign-in to Annals to complete your purchase.

buy this article subscribe

Access to EPUBs and PDFs for FREE Annals content requires users to be registered and logged in. A subscription is not required. You can create a free account below or from the following link. You will be redirected to acponline.org to create an account that will provide access to Annals. If you are accessing the Free Annals content via your institution's access, registration is not required.

Create your Free Account

You will be redirected to acponline.org to create an account that will provide access to Annals.

create account learn more

See Also

Related in ACP Journals

View options

PDF/EPUB

View PDF/EPUB

Related in ACP Journals

Full Text

View Full Text

Figures

Tables

Media

Share

Share

Copy the content Link

Share on social media

View full text|Download PDF