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Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.
Monday,2024-05-13 14:03 America/Los_Angeles — ecterry
| Title | Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits. |
| Publication Type | Journal Article |
| Year of Publication | 2024 |
| 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, Sundström, J, Langenberg, C, Tobin, MD, Giedraitis, V, Luan, J'an, Tuomilehto, J, Kutalik, Z, Ripatti, S, Salomaa, V, Girotto, G, Trompet, S, J Jukema, W, 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, MPina, Catamo, E, Cocca, M, Li-Gao, R, Hofer, E, Schmidt, H, Spedicati, B, Waldenberger, M, Strachan, DP, Laan, M, Teumer, A, Dörr, M, Gudnason, V, Cook, JP, Ruggiero, D, Kolcic, I, Boerwinkle, E, Traglia, M, Lehtimäki, 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 |
| Corporate/Institutional Authors | Million Veteran Program, LifeLines Cohort Study,, CHARGE Consortium,, ICBP Consortium, |
| Journal | Nat Genet |
| Date Published | 2024 Apr 30 |
| ISSN | 1546-1718 |
| Abstract | <p>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) 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) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10) 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). 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.</p> |
| DOI | 10.1038/s41588-024-01714-w |
| Alternate Journal | Nat Genet |
| PubMed ID | 38689001 |
| PubMed Central ID | 4979614 |
ePub date:
24/04