Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
| Title: | Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits |
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| Authors: | Keaton JM; Kamali Z; Xie T; Vaez A; Williams A; Goleva SB; Ani A; Evangelou E; Hellwege JN; Yengo L; Young WJ; Traylor M; Giri A; Zheng Z; Zeng J; Chasman DI; Morris AP; Caulfield MJ; Hwang S-J; Kooner JS; Conen D; Attia JR; Morrison AC; Loos RJF; Kristiansson K; Schmidt R; Hicks AA; Pramstaller PP; Nelson CP; Samani NJ; Risch L; Gyllensten U; Melander O; Riese H; Wilson JF; Campbell H; Rich SS; Psaty BM; Lu Y; Rotter JI; Guo X; Rice KM; Vollenweider P; Sundstrom J; Langenberg C; Tobin MD; Giedraitis V; Luan J; Tuomilehto J; Kutalik Z; Ripatti S; Salomaa V; Girotto G; Trompet S; Jukema JW; van der Harst P; Ridker PM; Giulianini F; Vitart V; Goel A; Watkins H; Harris SE; Deary IJ; van der Most PJ; Oldehinkel AJ; Keavney BD; Hayward C; Campbell A; Boehnke M; Scott LJ; Boutin T; Mamasoula C; Jarvelin M-R; Peters A; Gieger C; Lakatta EG; Cucca F; Hui J; Knekt P; Enroth S; De Borst MH; Polasek O; Concas MP; Catamo E; Cocca M; Li-Gao R; Hofer E; Schmidt H; Spedicati B; Waldenberger M; Strachan DP; Laan M; Teumer A; Dorr M; Gudnason V; Cook JP; Ruggiero D; Kolcic I; Boerwinkle E; Traglia M; Lehtimaki T; Raitakari OT; Johnson AD; Newton-Cheh C; Brown MJ; Dominiczak AF; Sever PJ; Poulter N; Chambers JC; Elosua R; Siscovick D; Esko T; Metspalu A; Strawbridge RJ; Laakso M; Hamsten A; Hottenga J-J; de Geus E; Morris AD; Palmer CNA; Nolte IM; Milaneschi Y; Marten J; Wright A; Zeggini E; Howson JMM; O'Donnell CJ; Spector T; Nalls MA; Simonsick EM; Liu Y; van Duijn CM; Butterworth AS; Danesh JN; Menni C; Wareham NJ; Khaw K-T; Sun YV; Wilson PWF; Cho K; Visscher PM; Denny JC; Levy D; Edwards TL; Munroe PB; Snieder H; Warren HR |
| Source: | Nature Genetics, 1 May 2024 |
| Publisher Information: | Springer Nature |
| Publication Year: | 2024 |
| Collection: | Newcastle University Library ePrints Service |
| Description: | © 2024. The Author(s). 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. |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf |
| Language: | unknown |
| Relation: | https://eprints.ncl.ac.uk/298754; https://eprints.ncl.ac.uk/fulltext.aspx?url=298754/22939D6D-33EF-453B-A3E2-7242E203921E.pdf&pub_id=298754 |
| Availability: | https://eprints.ncl.ac.uk/298754 |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: | edsbas.EE8B8222 |
| Database: | BASE |