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Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk
journal contribution
posted on 2016-12-13, 09:46 authored by L. V. Taylor, H. R. Warren, E. Evangelou, C. P. Cabrera, H. Gao, M. Ren, B. Mifsud, I. Ntalla, P. Surendran, C. Liu, J. P. Cook, A. Kraja, F. Drenos, M. Loh, N. Verweij, J. Marten, I. Karaman, M. P. S. Lepe, P. O’Reilly, J. Knight, H. Snieder, N. Kato, J. He, E. S. Tai, A. M. Said, D. Porteous, M. Alver, N. Poulter, M. Farrall, R. T. Gansevoort, S. Padmanabhan, R. Mägi, A. Stanton, J. Connell, S. J. L. Bakker, A. Metspalu, D. Shields, S. Thom, M. Brown, P. Sever, T. Esko, C. Hayward, P. van der Harst, D. Saleheen, R. Chowdhury, J. C. Chambers, D. I. Chasman, A. Chakravarti, C. Newton-Cheh, C. M. Lindgren, D. Levy, J. S. Kooner, B. Keavney, M. Tomaszewski, Nilesh J. Samani, J. M. M. Howson, Martin D. Tobin, P. B. Munroe, G. B. Ehret, Louise V. Wain, M. R. Barnes, I. Tzoulaki, M. J. Caulfield, P. ElliottElevated 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, leading to discovery and validation of 107 novel loci. We also identify new
independent variants at 11 previously reported blood pressure loci. Combined 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 variants on future
cardiovascular disease risk.
Funding
HRW, CPC, MR, MRB, PBM, MB and MJC were funded by the National Institutes 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. HG was funded by the NIHR Imperial College Health Care NHS Trust and Imperial College London Biomedical Research Centre. MR was a recipient from China Scholarship Council (No. 2011632047). BM holds an MRC eMedLab Medical Bioinformatics Career Development Fellowship, funded from award MR/L016311/1. JMMH 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), European Commission Framework Programme 7 (HEALTH-F2-2012-279233). BK holds a British Heart Foundation Personal Chair. NJS holds a chair funded by the British Heart Foundation and is a NIHR Senior Investigator. FD was funded by the MRC Unit at the University of Bristol (MC_UU_12013/1-9). PSu was funded by the UK Medical Research Council (G0800270). CL and AK were funded by the NHLBI intramural funding. CNC was funded by the National Institutes of Health (HL113933, HL124262). PVDH was funded by the ZonMw grant 90.700.441, Marie Sklodowska-Curie GF (call: H2020- MSCA-IF-2014, Project ID: 661395). NV was supported by Marie Sklodowska-Curie GF grant (661395) and ICIN-NHI. NP received funding from the UK National Institute for Health Research Biomedical Research Centre funding scheme and also from his Senior Investigator Award. 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). PE is Director of the MRC-PHE Centre for Environment and Health and acknowledges support from the Medical Research Council and Public Health Engla
History
Citation
Nature Genetics, 2017, 49(3), pp.403-415.Alternative title
Discovery and validation of 107 blood pressure loci from UK Biobank offers novel biological insights into cardiovascular riskAuthor affiliation
/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Health SciencesVersion
- AM (Accepted Manuscript)
