Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.
Warren HR., Evangelou E., Cabrera CP., Gao H., Ren M., Mifsud B., Ntalla I., Surendran P., Liu C., Cook JP., Kraja AT., Drenos F., Loh M., Verweij N., Marten J., Karaman I., Lepe MP., O'Reilly PF., Knight J., Snieder H., Kato N., He J., Tai ES., Said MA., Porteous D., Alver M., Poulter N., Farrall M., Gansevoort RT., Padmanabhan S., Mägi R., Stanton A., Connell J., Bakker SJ., Metspalu A., Shields DC., Thom S., Brown M., Sever P., Esko T., Hayward C., van der Harst P., Saleheen D., Chowdhury R., Chambers JC., Chasman DI., Chakravarti A., Newton-Cheh C., Lindgren CM., Levy D., Kooner JS., Keavney B., Tomaszewski M., Samani NJ., Howson JM., Tobin MD., Munroe PB., Ehret GB., Wain LV., International Consortium of Blood Pressure (ICBP) 1000G Analyses None., BIOS Consortium None., Lifelines Cohort Study None., Understanding Society Scientific group None., CHD Exome+ Consortium None., ExomeBP Consortium None., T2D-GENES Consortium None., GoT2DGenes Consortium None., Cohorts for Heart and Ageing Research in Genome Epidemiology (CHARGE) BP Exome Consortium None., International Genomics of Blood Pressure (iGEN-BP) Consortium None., Barnes MR., Tzoulaki I., Caulfield MJ., Elliott P., UK Biobank CardioMetabolic Consortium BP working group None.
Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.