Secondary findings from clinical genomic sequencing: prevalence, patient perspectives, family history assessment, and health-care costs from a multisite study

被引：108

作者：

Hart, M. Ragan ^{[1
,2
]}

Biesecker, Barbara B. ^{[3
]}

Blout, Carrie L. ^{[4
]}

Christensen, Kurt D. ^{[4
,5
]}

Amendola, Laura M. ^{[1
,2
]}

Bergstrom, Katie L. ^{[6
]}

Biswas, Sawona ^{[7
]}

Bowling, Kevin M. ^{[8
]}

Brothers, Kyle B. ^{[9
]}

Conlin, Laura K. ^{[10
,11
]}

Cooper, Greg M. ^{[8
]}

Dulik, Matthew C. ^{[10
,11
]}

East, Kelly M. ^{[8
]}

Everett, Jessica N. ^{[12
,13
]}

Finnila, Candice R. ^{[8
]}

Ghazani, Arezou A. ^{[14
]}

Gilmore, Marian J. ^{[15
]}

Goddard, Katrina A. B. ^{[16
]}

Jarvik, Gail P. ^{[1
,2
]}

Johnston, Jennifer J. ^{[17
]}

Kauffman, Tia L. ^{[16
]}

Kelley, Whitley V. ^{[8
]}

Krier, Joel B. ^{[4
]}

Lewis, Katie L. ^{[17
]}

McGuire, Amy L. ^{[18
]}

McMullen, Carmit ^{[16
]}

Ou, Jeffrey ^{[2
]}

Plon, Sharon E. ^{[6
]}

Rehm, Heidi L. ^{[5
,19
,20
]}

Richards, C. Sue ^{[21
]}

Romasko, Edward J. ^{[10
]}

Sagardia, Ane Miren ^{[3
]}

Spinner, Nancy B. ^{[10
]}

Thompson, Michelle L. ^{[8
]}

Turbitt, Erin ^{[3
]}

Vassy, Jason L. ^{[4
,5
,22
]}

Wilfond, Benjamin S. ^{[23
,24
]}

Veenstra, David L. ^{[2
,25
]}

Berg, Jonathan S. ^{[26
]}

Green, Robert C. ^{[4
,5
,20
,27
]}

Biesecker, Leslie G. ^{[17
]}

Hindorff, Lucia A. ^{[28
]}

机构：

[1] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA

[2] Univ Washington, Clin Sequencing Exploratory Res Coordinating Ctr, Seattle, WA 98195 USA

[3] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA

[4] Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA

[5] Harvard Med Sch, Boston, MA 02115 USA

[6] Baylor Coll Med, Dept Pediat, Oncol Sect, Houston, TX 77030 USA

[7] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA

[8] HudsonAlpha Inst Biotechnol, Huntsville, AL USA

[9] Univ Louisville, Dept Pediat, Louisville, KY 40292 USA

[10] Childrens Hosp, Dept Pathol & Lab Med, Div Genom Diagnost, Philadelphia, PA 19104 USA

[11] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA

[12] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[13] Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA

[14] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[15] Kaiser Permanente Northwest, Dept Med Genet, Portland, OR USA

[16] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA

[17] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA

[18] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA

[19] Partners HealthCare, Lab Mol Med, Cambridge, MA USA

[20] Broad Inst MIT & Harvard, Cambridge, MA USA

[21] Oregon Hlth & Sci Univ, Knight Diagnost Labs, Portland, OR USA

[22] VA Boston Healthcare Syst, Boston, MA USA

[23] Univ Washington, Dept Pediat, Seattle, WA 98195 USA

[24] Univ Washington, Seattle Childrens Res Inst, Seattle, WA 98195 USA

[25] Univ Washington, Dept Pharm, Seattle, WA 98195 USA

[26] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA

[27] Partners Personalized Med, Boston, MA USA

[28] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA

来源：

GENETICS IN MEDICINE | 2019年 / 21卷 / 05期

关键词：

genomic sequencing; secondary findings; health-care resource utilization; RANDOMIZED CONTROLLED-TRIAL; INCIDENTAL FINDINGS; MEDICAL GENETICS; AMERICAN-COLLEGE; EXOME; RECOMMENDATIONS; VARIANTS; DESIGN;

D O I：

10.1038/s41436-018-0308-x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Purpose: Clinical sequencing emerging in health care may result in secondary findings (SFs). Methods: Seventy-four of 6240 (1.2%) participants who underwent genome or exome sequencing through the Clinical Sequencing Exploratory Research (CSER) Consortium received one or more SFs from the original American College of Medical Genetics and Genomics (ACMG) recommended 56 gene-condition pair list; we assessed clinical and psychosocial actions. Results: The overall adjusted prevalence of SFs in the ACMG 56 genes across the CSER consortium was 1.7%. Initially 32% of the family histories were positive, and post disclosure, this increased to 48%. The average cost of follow-up medical actions per finding up to a 1-year period was $128 (observed, range: $0-$678) and $421 (recommended, range: $141-$1114). Case reports revealed variability in the frequency of and follow-up on medical recommendations patients received associated with each SF gene-condition pair. Participants did not report adverse psychosocial impact associated with receiving SFs; this was corroborated by 18 participant (or parent) interviews. All interviewed participants shared findings with relatives and reported that relatives did not pursue additional testing or care. Conclusion: Our results suggest that disclosure of SFs shows little to no adverse impact on participants and adds only modestly to near-term health-care costs; additional studies are needed to confirm these findings.

引用

页码：1100 / 1110

页数：11

共 32 条

[1] Actionable exomic incidental findings in 6503 participants: challenges of variant classification
Amendola, Laura M.
Dorschner, Michael O.
Robertson, Peggy D.
Salama, Joseph S.
Hart, Ragan
Shirts, Brian H.
Murray, Mitzi L.
Tokita, Mari J.
Gallego, Carlos J.
Kim, Daniel Seung
Bennett, James T.
Crosslin, David R.
Ranchalis, Jane
Jones, Kelly L.
Rosenthal, Elisabeth A.
Jarvik, Ella R.
Itsara, Andy
Turner, Emily H.
Herman, Daniel S.
Schleit, Jennifer
Burt, Amber
Jamal, Seema M.
Abrudan, Jenica L.
Johnson, Andrew D.
Conlin, Laura K.
Dulik, Matthew C.
Santani, Avni
Metterville, Danielle R.
Kelly, Melissa
Foreman, Ann Katherine M.
Lee, Kristy
Taylor, Kent D.
Guo, Xiuqing
Crooks, Kristy
Kiedrowski, Lesli A.
Raffe, Leslie J.
Gordon, Ora
Machini, Kalotina
Desnick, Robe
Biesecker, Leslie G.
Lubitz, Steven A.
Mulchandani, Surabhi
Cooper, Greg M.
Joffe, Steven
Richards, C. Sue
Yang, Yaoping
Rotter, Jerome I.
Rich, Stephen S.
O'Donne, Christopher J.
Berg, Jonathan S.
[J]. GENOME RESEARCH, 2015, 25 (03) : 305 - 315
[2] The cost-effectiveness of returning incidental findings from next-generation genomic sequencing
Bennette, Caroline S.
Gallego, Carlos J.
Burke, Wylie
Jarvik, Gail P.
Veenstra, David L.
[J]. GENETICS IN MEDICINE, 2015, 17 (07) : 587 - 595
[3] Berg JS, 2013, GENET MED, V15, P860, DOI 10.1038/gim.2013.133
[4] Biesecker LG, 2014, NEW ENGL J MED, V370, P2418, DOI [10.1056/NEJMra1312543, 10.1056/NEJMc1408914]
[5] The ClinSeq Project: Piloting large-scale genome sequencing for research in genomic medicine
Biesecker, Leslie G.
Mullikin, James C.
Facio, Flavia M.
Turner, Clesson
Cherukuri, Praveen F.
Blakesley, Robert W.
Bouffard, Gerard G.
Chines, Peter S.
Cruz, Pedro
Hansen, Nancy F.
Teer, Jamie K.
Maskeri, Baishali
Young, Alice C.
Manolio, Teri A.
Wilson, Alexander F.
Finkel, Toren
Hwang, Paul
Arai, Andrew
Remaley, Alan T.
Sachdev, Vandana
Shamburek, Robert
Cannon, Richard O.
Green, Eric D.
[J]. GENOME RESEARCH, 2009, 19 (09) : 1665 - 1674
[6] Bowling KM, 2017, GENOME MED, V9
[7] Recommendations for returning genomic incidental findings? We need to talk!
Burke, Wylie
Antommaria, Armand H. Matheny
Bennett, Robin
Botkin, Jeffrey
Clayton, Ellen Wright
Henderson, Gail E.
Holm, Ingrid A.
Jarvik, Gail P.
Khoury, Muin J.
Knoppers, Bartha Maria
Press, Nancy A.
Ross, Lainie Friedman
Rothstein, Mark A.
Saal, Howard
Uhlmann, Wendy R.
Wilfond, Benjamin
Wolf, Susan M.
Zimmern, Ron
[J]. GENETICS IN MEDICINE, 2013, 15 (11) : 854 - 859
[8] Anticipated responses of early adopter genetic specialists and nongenetic specialists to unsolicited genomic secondary findings
Christensen, Kurt D.
Bernhardt, Barbara A.
Jarvik, Gail P.
Hindorff, Lucia A.
Ou, Jeffrey
Biswas, Sawona
Powell, Bradford C.
Grundmeier, Robert W.
Machini, Kalotina
Karavite, Dean J.
Pennington, Jeffrey W.
Krantz, Ian D.
Berg, Jonathan S.
Goddard, Katrina A. B.
[J]. GENETICS IN MEDICINE, 2018, 20 (10) : 1186 - 1195
[9] Short-term costs of integrating whole-genome sequencing into primary care and cardiology settings: a pilot randomized trial
Christensen, Kurt D.
Vassy, Jason L.
Phillips, Kathryn A.
Blout, Carrie L.
Azzariti, Danielle R.
Lu, Christine Y.
Robinson, Jill O.
Lee, Kaitlyn
Douglas, Michael P.
Yeh, Jennifer M.
Machini, Kalotina
Stout, Natasha K.
Rehm, Heidi L.
McGuire, Amy L.
Green, Robert C.
Dukhovny, Dmitry
Bates, David W.
Cirino, Allison L.
Ho, Carolyn Y.
Krier, Joel B.
Lane, William J.
Lehmann, Lisa S.
MacRae, Calum A.
Morton, Cynthia C.
Seidman, Christine E.
Sunyaev, Shamil R.
Nguyen, Tiffany
Steffens, Eleanor
Betting, Wendi Nicole
Aronson, Samuel J.
Ceyhan-Birsoy, Ozge
Lebo, Matthew S.
McLaughlin, Heather M.
Tsai, Ellen A.
Blumenthal-Barby, Jennifer
Lee, Kai
Peoples, Hayley
Diamond, Pamela M.
Davis, Kelly
Ubel, Peter A.
Kraft, Peter
Roberts, J. Scott
Garber, Judy E.
Hambuch, Tina
Murray, Michael F.
Kohane, Isaac
Kong, Sek Won
[J]. GENETICS IN MEDICINE, 2018, 20 (12) : 1544 - 1553
[10] Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR Study
Dewey, Frederick E.
Murray, Michael F.
Overton, John D.
Habegger, Lukas
Leader, Joseph B.
Fetterolf, Samantha N.
O'Dushlaine, Colm
Van Hout, Cristopher V.
Staples, Jeffrey
Gonzaga-Jauregui, Claudia
Metpally, Raghu
Pendergrass, Sarah A.
Giovanni, Monica A.
Kirchner, H. Lester
Balasubramanian, Suganthi
Abul-Husn, Noura S.
Hartzel, Dustin N.
Lavage, Daniel R.
Kost, Korey A.
Packer, Jonathan S.
Lopez, Alexander E.
Penn, John
Mukherjee, Semanti
Gosalia, Nehal
Kanagaraj, Manoj
Li, Alexander H.
Mitnaul, Lyndon J.
Adams, Lance J.
Person, Thomas N.
Praveen, Kavita
Marcketta, Anthony
Lebo, Matthew S.
Austin-Tse, Christina A.
Mason-Suares, Heather M.
Bruse, Shannon
Mellis, Scott
Phillips, Robert
Stahl, Neil
Murphy, Andrew
Economides, Aris
Skelding, Kimberly A.
Still, Christopher D.
Elmore, James R.
Borecki, Ingrid B.
Yancopoulos, George D.
Davis, F. Daniel
Faucett, William A.
Gottesman, Omri
Ritchie, Marylyn D.
Shuldiner, Alan R.
[J]. SCIENCE, 2016, 354 (6319)

← 1 2 3 4 →