The impact of whole-genome sequencing on the primary care and outcomes of healthy adult patients: A pilot randomized trial

Annals of Internal Medicine

Volumn 167, Issue 3, 2017, Pages 159-169

  Vassy, Jason L ^a,c   Christensen, Kurt D ^b,c   Schonman, Erica F ^b,c   Blout, Carrie L ^b,c   Robinson, Jill O ^b,e   Krier, Joel B ^b,c   Diamond, Pamela M ^b,f   Lebo, Matthew S ^d   Machini, Kalotina ^b,d   Azzariti, Danielle R ^b,d   Dukhovny, Dmitry ^b,h   Bates, David W ^b,c   MacRae, Calum A ^b,c   Murray, Michael F ^b,m   Rehm, Heidi L ^b,d   McGuire, Amy L ^b,e   Green, Robert C ^b,c   Cirino, Allison L ^c   Ho, Carolyn Y ^c   Lane, William J ^c   Lehmann, Lisa S ^c   Morton, Cynthia C ^c   Perry, Denise L ^c   Seidman, Christine E ^c   Sunyaev, Shamil R ^c   Nguyen, Tiffany ^c   Steffens, Eleanor ^c   Betting, Wendi Nicole ^c   Aronson, Samuel J ^d   Ceyhan Birsoy, Ozge ^d   McLaughlin, Heather M ^d   Tsai, Ellen A ^d   Blumenthal Barby, Jennifer ^e   Feuerman, Lindsay Z ^e   Lee, Kaitlyn ^e   Slashinski, Melody J ^e   Davis, Kelly ^g   Ubel, Peter A ^g   Kraft, Peter ⁱ   Roberts, J Scott ^j   Garber, Judy E ^k   Hambuch, Tina ^l   Kohane, Isaac ⁿ   Kong, Sek Won ⁿ   more..

^a VA BOSTON HEALTHCARE SYSTEM   (United States)

^b Building for Transformative Medicine ^*  (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d LABORATORY FOR MOLECULAR MEDICINE   (United States)

^e BAYLOR COLLEGE OF MEDICINE   (United States)

^f UNIVERSITY OF TEXAS SCHOOL OF PUBLIC HEALTH   (United States)

^g DUKE UNIVERSITY   (United States)

^h OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

ⁱ HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^j UNIVERSITY OF MICHIGAN   (United States)

^k DANA FARBER CANCER INSTITUTE   (United States)

^l ILLUMINA INC   (United States)

^m GEISINGER HEALTH SYSTEM   (United States)

ⁿ BOSTON CHILDREN S HOSPITAL   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ADULT; AGED; ARTICLE; CARDIOMETABOLIC RISK; CLINICAL OUTCOME; EYE FUNDUS ALBIPUNCTATUS; FAMILY HISTORY; FEMALE; GENE; GENERAL PRACTITIONER; GENETIC VARIABILITY; HEALTH CARE COST; HEALTH CARE UTILIZATION; HUMAN; MAJOR CLINICAL STUDY; MALE; PATIENT-REPORTED OUTCOME; PHARMACOGENOMICS; PILOT STUDY; PRIMARY MEDICAL CARE; PRIORITY JOURNAL; RISK; STANDARD; VERY ELDERLY; WHOLE GENOME SEQUENCING; ANAMNESIS; ASYMPTOMATIC DISEASE; CONTROLLED STUDY; ECONOMICS; HEALTH BEHAVIOR; MIDDLE AGED; PATIENT ATTITUDE; PATIENT REFERRAL; PRIMARY HEALTH CARE; PROCEDURES; RANDOMIZED CONTROLLED TRIAL; RISK ASSESSMENT;

ADULT; AGED; ASYMPTOMATIC DISEASES; FEMALE; HEALTH BEHAVIOR; HEALTH CARE COSTS; HUMANS; MALE; MEDICAL HISTORY TAKING; MIDDLE AGED; PATIENT ACCEPTANCE OF HEALTH CARE; PATIENT REPORTED OUTCOME MEASURES; PILOT PROJECTS; PRIMARY HEALTH CARE; REFERRAL AND CONSULTATION; RISK ASSESSMENT; WHOLE GENOME SEQUENCING;

EID: 85026656059     PISSN: 00034819     EISSN: 15393704     Source Type: Journal    
DOI: 10.7326/M17-0188     Document Type: Article

References (41)

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
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
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
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
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
6. Relling MV, Evans WE. Pharmacogenomics in the clinic. Nature. 2015;526:343-50. [PMID: 26469045] doi:10.1038/nature15817
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
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
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
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
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
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
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
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.
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
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
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
18. Snaith RP, Zigmond AS. The hospital anxiety and depression scale [Letter]. Br Med J (Clin Res Ed). 1986;292:344. [PMID: 3080166]
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]
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
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.
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]
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]
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
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
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
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
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
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
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
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
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
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
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
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;89:8.16.1-8.16.23. [PMID: 27037489] doi:10.1002/0471142905.hg0816s89
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
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
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
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
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
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