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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. Elliott
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, 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 risk

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Health Sciences

Version

  • AM (Accepted Manuscript)

Published in

Nature Genetics

Publisher

Nature Publishing Group

issn

1061-4036

eissn

1546-1718

Acceptance date

2016-12-01

Copyright date

2017

Available date

2017-07-30

Publisher version

https://www.ncbi.nlm.nih.gov/pubmed/28135244

Notes

The file associated with this record is under embargo until 6 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en

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