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. ; H.R.W., C.P.C., M.R., M.R.B., P.B.M., M.B. and M.J.C. were funded by the National Institute for Health Research (NIHR) as part of the portfolio of translational research of the NIHR Biomedical Research Unit at Barts and The London School of Medicine and Dentistry. H.G. was funded by the NIHR Imperial College Health Care NHS Trust and Imperial College London Biomedical Research Centre. M.R. was a recipient of a grant from the China Scholarship Council (2011632047). B.M. holds an MRC eMedLab Medical Bioinformatics Career Development Fellowship, funded from award MR/L016311/1. J.M.M.H. was funded by the UK Medical Research Council (G0800270), British Heart Foundation (SP/09/002), UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (268834) and European Commission Framework Programme 7 (HEALTH-F2-2012-279233). B.K. holds a British Heart Foundation Personal Chair (CH/13/2/30154). N.J.S. holds a chair funded by the British Heart Foundation and is an NIHR Senior Investigator. F.D. was funded by the MRC Unit at the University of Bristol (MC_UU_12013/1-9). P. Surendran was funded by the UK Medical Research Council (G0800270). C.L. and A.K. were funded by NHLBI intramural funding. C.N.-C. was funded by the National Institutes of Health (HL113933, HL124262). P.v.d.H. was funded by ZonMw grant 90.700.441, Marie Sklodowska-Curie GF (call, H2020-MSCA-IF-2014; project ID, 661395). N.V. was supported by a Marie Sklodowska-Curie GF grant (661395) and ICIN-NHI. N.P. received funding from the UK National Institute for Health Research Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London and also from his Senior Investigator Award. P. Sever was supported by the NIHR Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London. S.T. was supported by the NIHR Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London. P.F.O'R. received funding from the UK Medical Research Council (MR/N015746/1) and the Wellcome Trust (109863/Z/15/Z). I.K. was supported by the EU PhenoMeNal project (Horizon 2020, 654241). A.C. was funded by the National Institutes of Health (HL128782, HL086694). M.F. was supported by a Wellcome Trust core award (090532/Z/09/Z) and the BHF Centre of Research Excellence, Oxford (RE/13/1/30181). C.H. was funded by an MRC core grant for QTL in Health and Disease programme. Some of this work used the ALICE and SPECTRE High-Performance Computing Facilities at the University of Leicester. M.J.C. is a National Institute for Health Research (NIHR) senior investigator. P.E. is a National Institute for Health Research (NIHR) senior investigator and acknowledges support from the NIHR Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London, and the NIHR Health Protection Research Unit in Health Impact of Environmental Hazards (HPRU-2012-10141). As director of the MRC-PHE Centre for Environment and Health, P.E. acknowledges support from the Medical Research Council and Public Health England (MR/L01341X/1). This work used the computing resources of the UK Medical Bioinformatics partnership–aggregation, integration, visualisation and analysis of large, complex data (UK MED-BIO), which is supported by the Medical Research Council (MR/L01632X/1). This research was supported by the British Heart Foundation (grant SP/13/2/30111). Project title: Large-Scale Comprehensive Genotyping of UK Biobank for Cardiometabolic Traits and Diseases: UK CardioMetabolic Consortium (UKCMC). This research has been conducted using the UK Biobank Resource under application number 236.