Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/c1d75398-a528-4d34-985b-b73697718d3f
- author
- Keaton, J.M.
; Melander, O.
LU
and Warren, H.R.
- author collaboration
- organization
- publishing date
- 2024
- 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 < 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}}, }