Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups

Nuzulul Kurniansyah; Matthew O. Goodman; Alyna T. Khan; Jiongming Wang; Elena Feofanova; Joshua C. Bis; Kerri L. Wiggins; Jennifer E. Huffman; Tanika Kelly; Tali Elfassy; Xiuqing Guo; Walter Palmas; Henry J. Lin; Shih Jen Hwang; Yan Gao; Kendra Young; Gregory L. Kinney; Jennifer A. Smith; Bing Yu; Simin Liu; Sylvia Wassertheil-Smoller; Jo Ann E. Manson; Xiaofeng Zhu; Yii Der Ida Chen; I. Te Lee; C. Charles Gu; Donald M. Lloyd-Jones; Sebastian Zöllner; Myriam Fornage; Charles Kooperberg; Adolfo Correa; Bruce M. Psaty; Donna K. Arnett; Carmen R. Isasi; Stephen S. Rich; Robert C. Kaplan; Susan Redline; Braxton D. Mitchell; Nora Franceschini; Daniel Levy; Jerome I. Rotter; Alanna C. Morrison; Tamar Sofer

doi:10.1038/s41467-023-38990-9

Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups

Nuzulul Kurniansyah, Matthew O. Goodman, Alyna T. Khan, Jiongming Wang, Elena Feofanova, Joshua C. Bis, Kerri L. Wiggins, Jennifer E. Huffman, Tanika Kelly, Tali Elfassy, Xiuqing Guo, Walter Palmas, Henry J. Lin, Shih Jen Hwang, Yan Gao, Kendra Young, Gregory L. Kinney, Jennifer A. Smith, Bing Yu, Simin LiuSylvia Wassertheil-Smoller, Jo Ann E. Manson, Xiaofeng Zhu, Yii Der Ida Chen, I. Te Lee, C. Charles Gu, Donald M. Lloyd-Jones, Sebastian Zöllner, Myriam Fornage, Charles Kooperberg, Adolfo Correa, Bruce M. Psaty, Donna K. Arnett, Carmen R. Isasi, Stephen S. Rich, Robert C. Kaplan, Susan Redline, Braxton D. Mitchell, Nora Franceschini, Daniel Levy, Jerome I. Rotter, Alanna C. Morrison, Tamar Sofer

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Abstract

We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare “clumping-and-thresholding” (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs developed from multiple independent GWAS, perform best across all race/ethnic backgrounds. Stratified analysis in All of Us shows that PRSs are better predictive of BP in females compared to males, individuals without obesity, and middle-aged (40-60 years) compared to older and younger individuals.

Original language	English
Article number	3202
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-38990-9
State	Published - Dec 2023

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Kurniansyah, N., Goodman, M. O., Khan, A. T., Wang, J., Feofanova, E., Bis, J. C., Wiggins, K. L., Huffman, J. E., Kelly, T., Elfassy, T., Guo, X., Palmas, W., Lin, H. J., Hwang, S. J., Gao, Y., Young, K., Kinney, G. L., Smith, J. A., Yu, B., ... Sofer, T. (2023). Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups. Nature communications, 14(1), Article 3202. https://doi.org/10.1038/s41467-023-38990-9

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title = "Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups",

abstract = "We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare “clumping-and-thresholding” (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs developed from multiple independent GWAS, perform best across all race/ethnic backgrounds. Stratified analysis in All of Us shows that PRSs are better predictive of BP in females compared to males, individuals without obesity, and middle-aged (40-60 years) compared to older and younger individuals.",

author = "Nuzulul Kurniansyah and Goodman, {Matthew O.} and Khan, {Alyna T.} and Jiongming Wang and Elena Feofanova and Bis, {Joshua C.} and Wiggins, {Kerri L.} and Huffman, {Jennifer E.} and Tanika Kelly and Tali Elfassy and Xiuqing Guo and Walter Palmas and Lin, {Henry J.} and Hwang, {Shih Jen} and Yan Gao and Kendra Young and Kinney, {Gregory L.} and Smith, {Jennifer A.} and Bing Yu and Simin Liu and Sylvia Wassertheil-Smoller and Manson, {Jo Ann E.} and Xiaofeng Zhu and Chen, {Yii Der Ida} and Lee, {I. Te} and Gu, {C. Charles} and Lloyd-Jones, {Donald M.} and Sebastian Z{\"o}llner and Myriam Fornage and Charles Kooperberg and Adolfo Correa and Psaty, {Bruce M.} and Arnett, {Donna K.} and Isasi, {Carmen R.} and Rich, {Stephen S.} and Kaplan, {Robert C.} and Susan Redline and Mitchell, {Braxton D.} and Nora Franceschini and Daniel Levy and Rotter, {Jerome I.} and Morrison, {Alanna C.} and Tamar Sofer",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-38990-9",

language = "English",

volume = "14",

journal = "Nature communications",

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Kurniansyah, N, Goodman, MO, Khan, AT, Wang, J, Feofanova, E, Bis, JC, Wiggins, KL, Huffman, JE, Kelly, T, Elfassy, T, Guo, X, Palmas, W, Lin, HJ, Hwang, SJ, Gao, Y, Young, K, Kinney, GL, Smith, JA, Yu, B, Liu, S, Wassertheil-Smoller, S, Manson, JAE, Zhu, X, Chen, YDI, Lee, IT, Gu, CC, Lloyd-Jones, DM, Zöllner, S, Fornage, M, Kooperberg, C, Correa, A, Psaty, BM, Arnett, DK, Isasi, CR, Rich, SS, Kaplan, RC, Redline, S, Mitchell, BD, Franceschini, N, Levy, D, Rotter, JI, Morrison, AC & Sofer, T 2023, 'Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups', Nature communications, vol. 14, no. 1, 3202. https://doi.org/10.1038/s41467-023-38990-9

TY - JOUR

T1 - Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups

AU - Kurniansyah, Nuzulul

AU - Goodman, Matthew O.

AU - Khan, Alyna T.

AU - Wang, Jiongming

AU - Feofanova, Elena

AU - Bis, Joshua C.

AU - Wiggins, Kerri L.

AU - Huffman, Jennifer E.

AU - Kelly, Tanika

AU - Elfassy, Tali

AU - Guo, Xiuqing

AU - Palmas, Walter

AU - Lin, Henry J.

AU - Hwang, Shih Jen

AU - Gao, Yan

AU - Young, Kendra

AU - Kinney, Gregory L.

AU - Smith, Jennifer A.

AU - Yu, Bing

AU - Liu, Simin

AU - Wassertheil-Smoller, Sylvia

AU - Manson, Jo Ann E.

AU - Zhu, Xiaofeng

AU - Chen, Yii Der Ida

AU - Lee, I. Te

AU - Gu, C. Charles

AU - Lloyd-Jones, Donald M.

AU - Zöllner, Sebastian

AU - Fornage, Myriam

AU - Kooperberg, Charles

AU - Correa, Adolfo

AU - Psaty, Bruce M.

AU - Arnett, Donna K.

AU - Isasi, Carmen R.

AU - Rich, Stephen S.

AU - Kaplan, Robert C.

AU - Redline, Susan

AU - Mitchell, Braxton D.

AU - Franceschini, Nora

AU - Levy, Daniel

AU - Rotter, Jerome I.

AU - Morrison, Alanna C.

AU - Sofer, Tamar

PY - 2023/12

Y1 - 2023/12

N2 - We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare “clumping-and-thresholding” (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs developed from multiple independent GWAS, perform best across all race/ethnic backgrounds. Stratified analysis in All of Us shows that PRSs are better predictive of BP in females compared to males, individuals without obesity, and middle-aged (40-60 years) compared to older and younger individuals.

AB - We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare “clumping-and-thresholding” (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs developed from multiple independent GWAS, perform best across all race/ethnic backgrounds. Stratified analysis in All of Us shows that PRSs are better predictive of BP in females compared to males, individuals without obesity, and middle-aged (40-60 years) compared to older and younger individuals.

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U2 - 10.1038/s41467-023-38990-9

DO - 10.1038/s41467-023-38990-9

M3 - Article

C2 - 37268629

AN - SCOPUS:85160892796

SN - 2041-1723

VL - 14

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 3202

ER -

Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups

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