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.

Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits / Keaton, J. M.; Kamali, Z.; Xie, T.; Vaez, A.; Williams, A.; Goleva, S. B.; Ani, A.; Evangelou, E.; Hellwege, J. N.; Yengo, L.; Young, W. J.; Traylor, M.; Giri, A.; Zheng, Z.; Zeng, J.; Chasman, D. I.; Morris, A. P.; Caulfield, M. J.; Hwang, S. -J.; Kooner, J. S.; Conen, D.; Attia, J. R.; Morrison, A. C.; Loos, R. J. F.; Kristiansson, K.; Schmidt, R.; Hicks, A. A.; Pramstaller, P. P.; Nelson, C. P.; Samani, N. J.; Risch, L.; Gyllensten, U.; Melander, O.; Riese, H.; Wilson, J. F.; Campbell, H.; Rich, S. S.; Psaty, B. M.; Lu, Y.; Rotter, J. I.; Guo, X.; Rice, K. M.; Vollenweider, P.; Sundstrom, J.; Langenberg, C.; Tobin, M. D.; Giedraitis, V.; Luan, J.; Tuomilehto, J.; Kutalik, Z.; Ripatti, S.; Salomaa, V.; Girotto, G.; Trompet, S.; Jukema, J. W.; van der Harst, P.; Ridker, P. M.; Giulianini, F.; Vitart, V.; Goel, A.; Watkins, H.; Harris, S. E.; Deary, I. J.; van der Most, P. J.; Oldehinkel, A. J.; Keavney, B. D.; Hayward, C.; Campbell, A.; Boehnke, M.; Scott, L. J.; Boutin, T.; Mamasoula, C.; Jarvelin, M. -R.; Peters, A.; Gieger, C.; Lakatta, E. G.; Cucca, F.; Hui, J.; Knekt, P.; Enroth, S.; De Borst, M. H.; Polasek, O.; Concas, M. P.; Catamo, E.; Cocca, M.; Li-Gao, R.; Hofer, E.; Schmidt, H.; Spedicati, B.; Waldenberger, M.; Strachan, D. P.; Laan, M.; Teumer, A.; Dorr, M.; Gudnason, V.; Cook, J. P.; Ruggiero, D.; Kolcic, I.; Boerwinkle, E.; Traglia, M.; Lehtimaki, T.; Raitakari, O. T.; Johnson, A. D.; Newton-Cheh, C.; Brown, M. J.; Dominiczak, A. F.; Sever, P. J.; Poulter, N.; Chambers, J. C.; Elosua, R.; Siscovick, D.; Esko, T.; Metspalu, A.; Strawbridge, R. J.; Laakso, M.; Hamsten, A.; Hottenga, J. -J.; de Geus, E.; Morris, A. D.; Palmer, C. N. A.; Nolte, I. M.; Milaneschi, Y.; Marten, J.; Wright, A.; Zeggini, E.; Howson, J. M. M.; O'Donnell, C. J.; Spector, T.; Nalls, M. A.; Simonsick, E. M.; Liu, Y.; van Duijn, C. M.; Butterworth, A. S.; Danesh, J. N.; Menni, C.; Wareham, N. J.; Khaw, K. -T.; Sun, Y. V.; Wilson, P. W. F.; Cho, K.; Visscher, P. M.; Denny, J. C.; Levy, D.; Edwards, T. L.; Munroe, P. B.; Snieder, H.; Warren, H. R.. - In: NATURE GENETICS. - ISSN 1546-1718. - 56:5(2024), pp. 778-791. [10.1038/s41588-024-01714-w]

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

Cucca F.;Liu Y.;
2024-01-01

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.
2024
Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits / Keaton, J. M.; Kamali, Z.; Xie, T.; Vaez, A.; Williams, A.; Goleva, S. B.; Ani, A.; Evangelou, E.; Hellwege, J. N.; Yengo, L.; Young, W. J.; Traylor, M.; Giri, A.; Zheng, Z.; Zeng, J.; Chasman, D. I.; Morris, A. P.; Caulfield, M. J.; Hwang, S. -J.; Kooner, J. S.; Conen, D.; Attia, J. R.; Morrison, A. C.; Loos, R. J. F.; Kristiansson, K.; Schmidt, R.; Hicks, A. A.; Pramstaller, P. P.; Nelson, C. P.; Samani, N. J.; Risch, L.; Gyllensten, U.; Melander, O.; Riese, H.; Wilson, J. F.; Campbell, H.; Rich, S. S.; Psaty, B. M.; Lu, Y.; Rotter, J. I.; Guo, X.; Rice, K. M.; Vollenweider, P.; Sundstrom, J.; Langenberg, C.; Tobin, M. D.; Giedraitis, V.; Luan, J.; Tuomilehto, J.; Kutalik, Z.; Ripatti, S.; Salomaa, V.; Girotto, G.; Trompet, S.; Jukema, J. W.; van der Harst, P.; Ridker, P. M.; Giulianini, F.; Vitart, V.; Goel, A.; Watkins, H.; Harris, S. E.; Deary, I. J.; van der Most, P. J.; Oldehinkel, A. J.; Keavney, B. D.; Hayward, C.; Campbell, A.; Boehnke, M.; Scott, L. J.; Boutin, T.; Mamasoula, C.; Jarvelin, M. -R.; Peters, A.; Gieger, C.; Lakatta, E. G.; Cucca, F.; Hui, J.; Knekt, P.; Enroth, S.; De Borst, M. H.; Polasek, O.; Concas, M. P.; Catamo, E.; Cocca, M.; Li-Gao, R.; Hofer, E.; Schmidt, H.; Spedicati, B.; Waldenberger, M.; Strachan, D. P.; Laan, M.; Teumer, A.; Dorr, M.; Gudnason, V.; Cook, J. P.; Ruggiero, D.; Kolcic, I.; Boerwinkle, E.; Traglia, M.; Lehtimaki, T.; Raitakari, O. T.; Johnson, A. D.; Newton-Cheh, C.; Brown, M. J.; Dominiczak, A. F.; Sever, P. J.; Poulter, N.; Chambers, J. C.; Elosua, R.; Siscovick, D.; Esko, T.; Metspalu, A.; Strawbridge, R. J.; Laakso, M.; Hamsten, A.; Hottenga, J. -J.; de Geus, E.; Morris, A. D.; Palmer, C. N. A.; Nolte, I. M.; Milaneschi, Y.; Marten, J.; Wright, A.; Zeggini, E.; Howson, J. M. M.; O'Donnell, C. J.; Spector, T.; Nalls, M. A.; Simonsick, E. M.; Liu, Y.; van Duijn, C. M.; Butterworth, A. S.; Danesh, J. N.; Menni, C.; Wareham, N. J.; Khaw, K. -T.; Sun, Y. V.; Wilson, P. W. F.; Cho, K.; Visscher, P. M.; Denny, J. C.; Levy, D.; Edwards, T. L.; Munroe, P. B.; Snieder, H.; Warren, H. R.. - In: NATURE GENETICS. - ISSN 1546-1718. - 56:5(2024), pp. 778-791. [10.1038/s41588-024-01714-w]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/346609
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 7
social impact