Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits

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

Standard

Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits. / Million Veteran Program; LifeLines Cohort Study; CHARGE Consortium; ICBP Consortium.

In: Nature Genetics, Vol. 56, No. 5, 2024, p. 778-791.

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

Harvard

Million Veteran Program, LifeLines Cohort Study, CHARGE Consortium & ICBP Consortium 2024, 'Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits', Nature Genetics, vol. 56, no. 5, pp. 778-791. https://doi.org/10.1038/s41588-024-01714-w

APA

Million Veteran Program, LifeLines Cohort Study, CHARGE Consortium, & ICBP Consortium (2024). Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits. Nature Genetics, 56(5), 778-791. https://doi.org/10.1038/s41588-024-01714-w

Vancouver

Million Veteran Program, LifeLines Cohort Study, CHARGE Consortium, ICBP Consortium. Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits. Nature Genetics. 2024;56(5):778-791. https://doi.org/10.1038/s41588-024-01714-w

Author

Million Veteran Program ; LifeLines Cohort Study ; CHARGE Consortium ; ICBP Consortium. / Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits. In: Nature Genetics. 2024 ; Vol. 56, No. 5. pp. 778-791.

Bibtex

@article{0bc5e66b5eb142778c3f56ebfa26e07e,
title = "Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits",
abstract = "Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.",
author = "Keaton, {Jacob M.} and Zoha Kamali and Tian Xie and Ahmad Vaez and Ariel Williams and Goleva, {Slavina B.} and Alireza Ani and Evangelos Evangelou and Hellwege, {Jacklyn N.} and Loic Yengo and Young, {William J.} and Matthew Traylor and Ayush Giri and Zhili Zheng and Jian Zeng and Chasman, {Daniel I.} and Morris, {Andrew P.} and Caulfield, {Mark J.} and Hwang, {Shih Jen} and Kooner, {Jaspal S.} and David Conen and Attia, {John R.} and Morrison, {Alanna C.} and Loos, {Ruth J.F.} and Kati Kristiansson and Reinhold Schmidt and Hicks, {Andrew A.} and Pramstaller, {Peter P.} and Nelson, {Christopher P.} and Samani, {Nilesh J.} and Lorenz Risch and Ulf Gyllensten and Olle Melander and Harriette Riese and Wilson, {James F.} and Harry Campbell and Rich, {Stephen S.} and Psaty, {Bruce M.} and Yingchang Lu and Rotter, {Jerome I.} and Xiuqing Guo and Rice, {Kenneth M.} and Peter Vollenweider and Johan Sundstr{\"o}m and Claudia Langenberg and Tobin, {Martin D.} and Vilmantas Giedraitis and Jian'an Luan and Jaakko Tuomilehto and Sun, {Yan V.} and {Million Veteran Program} and {LifeLines Cohort Study} and {CHARGE Consortium} and {ICBP Consortium}",
note = "Publisher Copyright: {\textcopyright} 2024. The Author(s).",
year = "2024",
doi = "10.1038/s41588-024-01714-w",
language = "English",
volume = "56",
pages = "778--791",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "5",

}

RIS

TY - JOUR

T1 - Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits

AU - Keaton, Jacob M.

AU - Kamali, Zoha

AU - Xie, Tian

AU - Vaez, Ahmad

AU - Williams, Ariel

AU - Goleva, Slavina B.

AU - Ani, Alireza

AU - Evangelou, Evangelos

AU - Hellwege, Jacklyn N.

AU - Yengo, Loic

AU - Young, William J.

AU - Traylor, Matthew

AU - Giri, Ayush

AU - Zheng, Zhili

AU - Zeng, Jian

AU - Chasman, Daniel I.

AU - Morris, Andrew P.

AU - Caulfield, Mark J.

AU - Hwang, Shih Jen

AU - Kooner, Jaspal S.

AU - Conen, David

AU - Attia, John R.

AU - Morrison, Alanna C.

AU - Loos, Ruth J.F.

AU - Kristiansson, Kati

AU - Schmidt, Reinhold

AU - Hicks, Andrew A.

AU - Pramstaller, Peter P.

AU - Nelson, Christopher P.

AU - Samani, Nilesh J.

AU - Risch, Lorenz

AU - Gyllensten, Ulf

AU - Melander, Olle

AU - Riese, Harriette

AU - Wilson, James F.

AU - Campbell, Harry

AU - Rich, Stephen S.

AU - Psaty, Bruce M.

AU - Lu, Yingchang

AU - Rotter, Jerome I.

AU - Guo, Xiuqing

AU - Rice, Kenneth M.

AU - Vollenweider, Peter

AU - Sundström, Johan

AU - Langenberg, Claudia

AU - Tobin, Martin D.

AU - Giedraitis, Vilmantas

AU - Luan, Jian'an

AU - Tuomilehto, Jaakko

AU - Sun, Yan V.

AU - Million Veteran Program

AU - LifeLines Cohort Study

AU - CHARGE Consortium

AU - ICBP Consortium

N1 - Publisher Copyright: © 2024. The Author(s).

PY - 2024

Y1 - 2024

N2 - Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.

AB - Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.

U2 - 10.1038/s41588-024-01714-w

DO - 10.1038/s41588-024-01714-w

M3 - Journal article

C2 - 38689001

AN - SCOPUS:85193458394

VL - 56

SP - 778

EP - 791

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 5

ER -

ID: 392987426