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

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Τίτλος: Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
Συγγραφείς: 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
Πηγή: Nature Genetics, 1 May 2024
Στοιχεία εκδότη: Springer Nature
Έτος έκδοσης: 2024
Συλλογή: Newcastle University Library ePrints Service
Περιγραφή: © 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.
Τύπος εγγράφου: article in journal/newspaper
Περιγραφή αρχείου: application/pdf
Γλώσσα: 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
Διαθεσιμότητα: https://eprints.ncl.ac.uk/298754
Rights: https://creativecommons.org/licenses/by/4.0/
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  Data: Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
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– Name: TitleSource
  Label: Source
  Group: Src
  Data: Nature Genetics, 1 May 2024
– Name: Publisher
  Label: Publisher Information
  Group: PubInfo
  Data: Springer Nature
– Name: DatePubCY
  Label: Publication Year
  Group: Date
  Data: 2024
– Name: Subset
  Label: Collection
  Group: HoldingsInfo
  Data: Newcastle University Library ePrints Service
– Name: Abstract
  Label: Description
  Group: Ab
  Data: &#169; 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 &lt; 5 &#215; 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 &#215; 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 &#215; 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 &#215; 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.
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: article in journal/newspaper
– Name: Format
  Label: File Description
  Group: SrcInfo
  Data: application/pdf
– Name: Language
  Label: Language
  Group: Lang
  Data: unknown
– Name: NoteTitleSource
  Label: Relation
  Group: SrcInfo
  Data: https://eprints.ncl.ac.uk/298754; https://eprints.ncl.ac.uk/fulltext.aspx?url=298754/22939D6D-33EF-453B-A3E2-7242E203921E.pdf&amp;pub_id=298754
– Name: URL
  Label: Availability
  Group: URL
  Data: https://eprints.ncl.ac.uk/298754
– Name: Copyright
  Label: Rights
  Group: Cpyrght
  Data: https://creativecommons.org/licenses/by/4.0/
– Name: AN
  Label: Accession Number
  Group: ID
  Data: edsbas.EE8B8222
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsbas&AN=edsbas.EE8B8222
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      – TitleFull: Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
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            – D: 01
              M: 01
              Type: published
              Y: 2024
          Identifiers:
            – Type: issn-locals
              Value: edsbas
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              Value: edsbas.oa
          Titles:
            – TitleFull: Nature Genetics, 1 May 2024
              Type: main
ResultId 1