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

ICBP Consortium; CHARGE consortium; Million Veteran Program; Lifelines Cohort Study

doi:10.1038/s41588-024-01714-w

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

ICBP Consortium
, CHARGE consortium
, Million Veteran Program
, Lifelines Cohort Study

National Institutes of Health
Vanderbilt University
University of Groningen
Isfahan University of Medical Sciences
Imperial College London
University of Ioannina
Foundation for Research and Technology-Hellas
University of Queensland
Queen Mary University of London
Barts Health NHS Trust
University of Oxford
Broad Institute
Brigham and Women’s Hospital
Harvard University
University of Manchester
National Heart Lung and Blood Institute’s and Boston University’s Framingham Heart Study
Boston University
Population Health Research Institute, Ontario
University of Newcastle
University of Texas Health Science Center at Houston
Icahn School of Medicine at Mount Sinai
University of Copenhagen
National Institute for Health and Welfare
Medical University of Graz
EURAC Research
University of Lübeck
University of Leicester
National Institute for Health and Care Research
Private University of the Principality of Liechtenstein
Dr. Risch Anstalt
Uppsala University
Lund University
University of Edinburgh
University of Virginia
University of Washington
The Lundquist Institute
University of Lausanne
University of New South Wales
University of Cambridge
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
University Hospitals of Leicester NHS Trust
University of Helsinki
King Abdulaziz University
Vrije Universiteit Amsterdam
Swiss Institute of Bioinformatics
University of Trieste
IRCCS Ospedale Infantile Burlo Garofolo - Trieste
Leiden University
Interuniversity Cardiology Institute of the Netherlands
Utrecht University
Manchester University NHS Foundation Trust
University of Michigan, Ann Arbor
Newcastle University
University of Oulu
Helmholtz Zentrum München - German Research Center for Environmental Health
Ludwig Maximilian University of Munich
National Research Council of Italy
Busselton Population Medical Research Institute
University of Western Australia
University of Split
Algebra University
German Centre for Cardiovascular Research
St. George's University of London
University of Tartu
University of Greifswald
Icelandic Heart Association
University of Iceland
University of Liverpool
IRCCS Istituto Neurologico Mediterraneo Neuromed - Pozzilli (IS)
Baylor College of Medicine
San Raffaele Scientific Institute
Fimlab Laboratories
Tampere University
University of Turku
Massachusetts General Hospital
University of Glasgow
Lee Kong Chian School of Medicine
Hospital del Mar
CIBER de Enfermedades Cardiovasculares
The University of Vic - Central University of Catalonia
New York Academy of Medicine
University of Tartu
Health Data Research UK
Karolinska Institutet
University of Eastern Finland
Amsterdam UMC
University of Dundee
Technical University of Munich
University of Cambridge
King's College London
DataTecnica LLC
Duke University
Wellcome Trust Sanger Institute
Department of Twin Research and Genetic Epidemiology
Emory University
VA Atlanta Healthcare System
Department of Veterans Affairs

Research output: Contribution to journal › Article › peer-review

82 Citations (Scopus)

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.

Original language	English
Pages (from-to)	778-791
Number of pages	14
Journal	Nature Genetics
Volume	56
Issue number	5
Early online date	Apr 2024
DOIs	https://doi.org/10.1038/s41588-024-01714-w
Publication status	Published - May 2024
Externally published	Yes

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10.1038/s41588-024-01714-w

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@article{95850744af524f7a89ab6c593ddd2a7f,

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 = "\{ICBP Consortium\} and \{CHARGE consortium\} and \{Million Veteran Program\} and \{Lifelines Cohort Study\} and 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{\textquoteright}an Luan and Jaakko Tuomilehto and Hottenga, \{Jouke Jan\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = may,

doi = "10.1038/s41588-024-01714-w",

language = "English",

volume = "56",

pages = "778--791",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

}

TY - JOUR

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

AU - ICBP Consortium

AU - CHARGE consortium

AU - Million Veteran Program

AU - Lifelines Cohort Study

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 - Hottenga, Jouke Jan

PY - 2024/5

Y1 - 2024/5

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.

UR - https://www.scopus.com/pages/publications/85193458394

U2 - 10.1038/s41588-024-01714-w

DO - 10.1038/s41588-024-01714-w

M3 - Article

C2 - 38689001

AN - SCOPUS:85193458394

SN - 1061-4036

VL - 56

SP - 778

EP - 791

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

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

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