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

Keaton, J.M. ; Melander, O. LU orcid and Warren, H.R. (2024) In Nature Genetics 56(5). p.778-791
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... (More)
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. (Less)
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author
; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Blood Pressure, Female, Genetic Predisposition to Disease, Genetic Risk Score, Genome-Wide Association Study, Humans, Hypertension, Male, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Factors, White People, blood pressure, Caucasian, female, genetic predisposition, genetic risk score, genetics, genome-wide association study, human, hypertension, male, multifactorial inheritance, risk factor, single nucleotide polymorphism
in
Nature Genetics
volume
56
issue
5
pages
14 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85193458394
ISSN
1546-1718
DOI
10.1038/s41588-024-01714-w
language
English
LU publication?
yes
id
c1d75398-a528-4d34-985b-b73697718d3f
date added to LUP
2024-08-22 10:29:20
date last changed
2024-08-22 10:29:20
@article{c1d75398-a528-4d34-985b-b73697718d3f,
  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 &lt; 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, J.M. and Melander, O. and Warren, H.R.}},
  issn         = {{1546-1718}},
  keywords     = {{Blood Pressure; Female; Genetic Predisposition to Disease; Genetic Risk Score; Genome-Wide Association Study; Humans; Hypertension; Male; Multifactorial Inheritance; Polymorphism, Single Nucleotide; Risk Factors; White People; blood pressure; Caucasian; female; genetic predisposition; genetic risk score; genetics; genome-wide association study; human; hypertension; male; multifactorial inheritance; risk factor; single nucleotide polymorphism}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{778--791}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Genetics}},
  title        = {{Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits}},
  url          = {{http://dx.doi.org/10.1038/s41588-024-01714-w}},
  doi          = {{10.1038/s41588-024-01714-w}},
  volume       = {{56}},
  year         = {{2024}},
}