Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network

Anna C.F. Lewis; Rex L. Chisholm; John J. Connolly; Edward D. Esplin; Joe Glessner; Adam Gordon; Robert C. Green; Hakon Hakonarson; Margaret Harr; Ingrid A. Holm; Gail P. Jarvik; Elizabeth Karlson; Eimear E. Kenny; Leah Kottyan; Niall Lennon; Jodell E. Linder; Yuan Luo; Lisa J. Martin; Emma Perez; Megan J. Puckelwartz; Laura J. Rasmussen-Torvik; Maya Sabatello; Richard R. Sharp; Jordan W. Smoller; Rene Sterling; Shannon Terek; Wei Qi Wei; Stephanie M. Fullerton

doi:10.1016/j.ajhg.2024.04.005

Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network

Anna C.F. Lewis, Rex L. Chisholm, John J. Connolly, Edward D. Esplin, Joe Glessner, Adam Gordon, Robert C. Green, Hakon Hakonarson, Margaret Harr, Ingrid A. Holm, Gail P. Jarvik, Elizabeth Karlson, Eimear E. Kenny, Leah Kottyan, Niall Lennon, Jodell E. Linder, Yuan Luo, Lisa J. Martin, Emma Perez, Megan J. PuckelwartzLaura J. Rasmussen-Torvik, Maya Sabatello, Richard R. Sharp, Jordan W. Smoller, Rene Sterling, Shannon Terek, Wei Qi Wei, Stephanie M. Fullerton

Research output: Contribution to journal › Review article › peer-review

6 Scopus citations

Abstract

The differential performance of polygenic risk scores (PRSs) by group is one of the major ethical barriers to their clinical use. It is also one of the main practical challenges for any implementation effort. The social repercussions of how people are grouped in PRS research must be considered in communications with research participants, including return of results. Here, we outline the decisions faced and choices made by a large multi-site clinical implementation study returning PRSs to diverse participants in handling this issue of differential performance. Our approach to managing the complexities associated with the differential performance of PRSs serves as a case study that can help future implementers of PRSs to plot an anticipatory course in response to this issue.

Original language	English
Pages (from-to)	999-1005
Number of pages	7
Journal	American Journal of Human Genetics
Volume	111
Issue number	6
DOIs	https://doi.org/10.1016/j.ajhg.2024.04.005
State	Published - 6 Jun 2024

Access to Document

10.1016/j.ajhg.2024.04.005

Cite this

Lewis, A. C. F., Chisholm, R. L., Connolly, J. J., Esplin, E. D., Glessner, J., Gordon, A., Green, R. C., Hakonarson, H., Harr, M., Holm, I. A., Jarvik, G. P., Karlson, E., Kenny, E. E., Kottyan, L., Lennon, N., Linder, J. E., Luo, Y., Martin, L. J., Perez, E., ... Fullerton, S. M. (2024). Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network. American Journal of Human Genetics, 111(6), 999-1005. https://doi.org/10.1016/j.ajhg.2024.04.005

@article{128c99ce32a444e8a483d396e40328f9,

title = "Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network",

abstract = "The differential performance of polygenic risk scores (PRSs) by group is one of the major ethical barriers to their clinical use. It is also one of the main practical challenges for any implementation effort. The social repercussions of how people are grouped in PRS research must be considered in communications with research participants, including return of results. Here, we outline the decisions faced and choices made by a large multi-site clinical implementation study returning PRSs to diverse participants in handling this issue of differential performance. Our approach to managing the complexities associated with the differential performance of PRSs serves as a case study that can help future implementers of PRSs to plot an anticipatory course in response to this issue.",

author = "Lewis, {Anna C.F.} and Chisholm, {Rex L.} and Connolly, {John J.} and Esplin, {Edward D.} and Joe Glessner and Adam Gordon and Green, {Robert C.} and Hakon Hakonarson and Margaret Harr and Holm, {Ingrid A.} and Jarvik, {Gail P.} and Elizabeth Karlson and Kenny, {Eimear E.} and Leah Kottyan and Niall Lennon and Linder, {Jodell E.} and Yuan Luo and Martin, {Lisa J.} and Emma Perez and Puckelwartz, {Megan J.} and Rasmussen-Torvik, {Laura J.} and Maya Sabatello and Sharp, {Richard R.} and Smoller, {Jordan W.} and Rene Sterling and Shannon Terek and Wei, {Wei Qi} and Fullerton, {Stephanie M.}",

note = "Publisher Copyright: {\textcopyright} 2024 American Society of Human Genetics",

year = "2024",

month = jun,

day = "6",

doi = "10.1016/j.ajhg.2024.04.005",

language = "English",

volume = "111",

pages = "999--1005",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "6",

}

Lewis, ACF, Chisholm, RL, Connolly, JJ, Esplin, ED, Glessner, J, Gordon, A, Green, RC, Hakonarson, H, Harr, M, Holm, IA, Jarvik, GP, Karlson, E, Kenny, EE, Kottyan, L, Lennon, N, Linder, JE, Luo, Y, Martin, LJ, Perez, E, Puckelwartz, MJ, Rasmussen-Torvik, LJ, Sabatello, M, Sharp, RR, Smoller, JW, Sterling, R, Terek, S, Wei, WQ & Fullerton, SM 2024, 'Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network', American Journal of Human Genetics, vol. 111, no. 6, pp. 999-1005. https://doi.org/10.1016/j.ajhg.2024.04.005

TY - JOUR

T1 - Managing differential performance of polygenic risk scores across groups

T2 - Real-world experience of the eMERGE Network

AU - Lewis, Anna C.F.

AU - Chisholm, Rex L.

AU - Connolly, John J.

AU - Esplin, Edward D.

AU - Glessner, Joe

AU - Gordon, Adam

AU - Green, Robert C.

AU - Hakonarson, Hakon

AU - Harr, Margaret

AU - Holm, Ingrid A.

AU - Jarvik, Gail P.

AU - Karlson, Elizabeth

AU - Kenny, Eimear E.

AU - Kottyan, Leah

AU - Lennon, Niall

AU - Linder, Jodell E.

AU - Luo, Yuan

AU - Martin, Lisa J.

AU - Perez, Emma

AU - Puckelwartz, Megan J.

AU - Rasmussen-Torvik, Laura J.

AU - Sabatello, Maya

AU - Sharp, Richard R.

AU - Smoller, Jordan W.

AU - Sterling, Rene

AU - Terek, Shannon

AU - Wei, Wei Qi

AU - Fullerton, Stephanie M.

PY - 2024/6/6

Y1 - 2024/6/6

N2 - The differential performance of polygenic risk scores (PRSs) by group is one of the major ethical barriers to their clinical use. It is also one of the main practical challenges for any implementation effort. The social repercussions of how people are grouped in PRS research must be considered in communications with research participants, including return of results. Here, we outline the decisions faced and choices made by a large multi-site clinical implementation study returning PRSs to diverse participants in handling this issue of differential performance. Our approach to managing the complexities associated with the differential performance of PRSs serves as a case study that can help future implementers of PRSs to plot an anticipatory course in response to this issue.

AB - The differential performance of polygenic risk scores (PRSs) by group is one of the major ethical barriers to their clinical use. It is also one of the main practical challenges for any implementation effort. The social repercussions of how people are grouped in PRS research must be considered in communications with research participants, including return of results. Here, we outline the decisions faced and choices made by a large multi-site clinical implementation study returning PRSs to diverse participants in handling this issue of differential performance. Our approach to managing the complexities associated with the differential performance of PRSs serves as a case study that can help future implementers of PRSs to plot an anticipatory course in response to this issue.

UR - http://www.scopus.com/inward/record.url?scp=85193430995&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2024.04.005

DO - 10.1016/j.ajhg.2024.04.005

M3 - Review article

C2 - 38688278

AN - SCOPUS:85193430995

SN - 0002-9297

VL - 111

SP - 999

EP - 1005

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 6

ER -

Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network

Abstract

Access to Document

Fingerprint

Cite this