Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.
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., 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., Järvelin M-R., Peters A., Gieger C., Lakatta EG., Cucca F., Hui J., Knekt P., Enroth S., De Borst MH., Polašek O., Concas MP., 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., Million Veteran Program None., Lifelines Cohort Study None., CHARGE consortium None., ICBP Consortium None., Levy D., Edwards TL., Munroe PB., Snieder H., Warren HR.
Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P -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.