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ACKNOWLEDGEMENTS: The Medman study was funded by the Department of Health for England and Wales and managed by a collaboration of the National Pharmaceutical Association, the Royal Pharmaceutical Society of Great Britain, the Company Chemist Association and the Co-operative Pharmacy Technical Panel, led by the Pharmaceutical Services Negotiating Committee. The research in this paper was undertaken while the lead author MT was undertaking a doctoral research fellowship jointly funded by the Economic and Social Research Council (ESRC) and the Medical Research Council (MRC). The Health Economics Research Unit (HERU), University of Aberdeen is funded by the Chief Scientific Office of the Scottish Government Health and Social Care Directorate.

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Acknowledgements This study was supported by a Medical Research Council UK grant (grant number G0800901), as a sub-study of Nitrites in Acute Myocardial Infarction. Thanks are due to Roger Staff, for invaluable advice regarding receiver operator characteristic analysis.

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Acknowledgements This study was supported by a Medical Research Council UK grant (grant number G0800901), as a sub-study of Nitrites in Acute Myocardial Infarction. Thanks are due to Roger Staff, for invaluable advice regarding receiver operator characteristic analysis.

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Acknowledgments The authors would like to thank the participants of the EPIC-Norfolk cohort. We thank the nutritionist team and data management team of the EPIC-Norfolk cohort. The EPIC-Norfolk study was supported by grants from the Medical Research Council and Cancer Research UK. Funders had no role in study design or interpretation of the findings.

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We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics and the Wellcome Trust Sanger Institute for the generation of the sequencing data. This work was funded by Wellcome Trust grant 090532/Z/09/Z (J.F.). Primary phenotyping of the mice was supported by the Mary Lyon Centre and Mammalian Genetics Unit (Medical Research Council, UK Hub grant G0900747 91070 and Medical Research Council, UK grant MC U142684172). D.A.B acknowledges support from NIH R01AR056280. The sleep work was supported by the state of Vaud (Switzerland) and the Swiss National Science Foundation (SNF 14694 and 136201 to P.F.). The ECG work was supported by the Netherlands CardioVascular Research Initiative (Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences) PREDICT project, InterUniversity Cardiology Institute of the Netherlands (ICIN; 061.02; C.A.R., C.R.B). Na Cai is supported by the Agency of Science, Technology and Research (A*STAR) Graduate Academy. The authors wish to acknowledge excellent technical assistance from: Ayako Kurioka, Leo Swadling, Catherine de Lara, James Ussher, Rachel Townsend, Sima Lionikaite, Ausra S. Lionikiene, Rianne Wolswinkel and Inge van der Made. We would like to thank Thomas M Keane and Anthony G Doran for their help in annotating variants and adding the FVB/NJ strain to the Mouse Genomes Project.

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We are grateful for the co-operation and assistance that we received from NHS staff in the co-ordinating centres and clinical sites. We thank the women who participated in TOMBOLA. The TOMBOLA trial was supported by the Medical Research Council (G9700808) and the NHS in England and Scotland. The TOMBOLA Group comprises the following: Grant-holders: University of Aberdeen and NHS Grampian, Aberdeen, Scotland: Maggie Cruickshank, Graeme Murray, David Parkin, Louise Smart, Eric Walker, Norman Waugh (Principal Investigator 2004–2008) University of Nottingham and Nottingham NHS, Nottingham, England: Mark Avis, Claire Chilvers, Katherine Fielding, Rob Hammond, David Jenkins, Jane Johnson, Keith Neal, Ian Russell, Rashmi Seth, Dave Whynes University of Dundee and NHS Tayside, Dundee, Tayside: Ian Duncan, Alistair Robertson (deceased) University of Ottawa, Ottawa, Canada: Julian Little (Principal Investigator 1999–2004) National Cancer Registry, Cork, Ireland: Linda Sharp Bangor University, Bangor, Wales: Ian Russell University of Hull, Hull, England: Leslie G Walker Staff in clinical sites and co-ordinating centres Grampian Breda Anthony, Sarah Bell, Adrienne Bowie, Katrina Brown (deceased), Joe Brown, Kheng Chew, Claire Cochran, Seonaidh Cotton, Jeannie Dean, Kate Dunn, Jane Edwards, David Evans, Julie Fenty, Al Finlayson, Marie Gallagher, Nicola Gray, Maureen Heddle, Alison Innes, Debbie Jobson, Mandy Keillor, Jayne MacGregor, Sheona Mackenzie, Amanda Mackie, Gladys McPherson, Ike Okorocha, Morag Reilly, Joan Rodgers, Alison Thornton, Rachel Yeats Tayside Lindyanne Alexander, Lindsey Buchanan, Susan Henderson, Tine Iterbeke, Susanneke Lucas, Gillian Manderson, Sheila Nicol, Gael Reid, Carol Robinson, Trish Sandilands Nottingham Marg Adrian, Ahmed Al-Sahab, Elaine Bentley, Hazel Brook, Claire Bushby, Rita Cannon, Brenda Cooper, Ruth Dowell, Mark Dunderdale, Dr Gabrawi, Li Guo, Lisa Heideman, Steve Jones, Salli Lawson, Zoë Philips, Christopher Platt, Shakuntala Prabhakaran, John Rippin, Rose Thompson, Elizabeth Williams, Claire Woolley Statistical analysis Seonaidh Cotton, Kirsten Harrild, John Norrie, Linda Sharp External Trial Steering Committee Nicholas Day (chair, 1999–2004), Theresa Marteau (chair 2004-), Mahesh Parmar, Julietta Patnick and Ciaran Woodman.

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TG and CF are funded by FEDER funds through the Operational Programme Competitiveness Factors e COMPETE and national funds by FCT e Foundation for Science and Technology under the strategic project UID/NEU/04539/2013. C.F. is a recipient of a postdoctoral fellowship from FCT-Fundac¸ ~ao para a Ci^encia e Tecnologia (SFRH/BPD/63733/2009). NG is funded by The Wellcome Trust (080088, 086827, 075470, 099215 & 097377), the FungiBrain Marie Curie Network and the Medical Research Council (UK).

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Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: G.T.J. and G.J.M. have received research funding from Pfizer and AbbVie. L.E.D. conducted the analysis while funded by an Medical Research Council PhD studentship

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Supported by Royal Society of London (University Research Fellowship), Medical Research Council (New Investigator Research Grant) and CNRS.

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Medical Research Council (ref G0701604) and administered by the NIHR-EME (ref 09-800-26)

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The NIHR BioResource-Rare Diseases and the ThromboGenomics sequencing projects are supported by the National Institute for Health Research (NIHR; http://www.nihr.ac.uk). KB is an NIHR academic clinical fellow. SKW is supported by a Medical Research Council (MRC) Clinical Training Fellowship (MR/K023489/1). KS and ET are supported by the NIHR BioResource Rare Diseases. CSW and NJM are supported by the British Heart Foundation (FS/11/2/28579). ADM is supported by the NIHR Bristol Cardiovascular Biomedical Research Unit.

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Abimbola Ayorinde’s PhD funded by the Medical Research Council. This study was funded by the British Pain Society (Mildred Clulow Award) and preparatory work by National Health Service Grampian.

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This work was supported by programme grants from the Medical Research Council G1000143 and the Cancer Research UK 8257. Funders have no roles in study design, analysis, and interpretation of the findings.

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Funding: Authors LH and MMW are part of the Healthy Children, Healthy Families Theme of the National Institute of Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) Yorkshire and Humber (www.clahrc-yh.nihr.ac.uk/). Please note, the views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR and the Department of Health. At different points in time this programme of research has been supported by a Medical Research Council (MRC; www.mrc.ac.uk) scholarship, an MRC Centenary Early Career Award and a grant from The Waterloo Foundation (TWF reference: 1285/1986; www.waterloofoundation.org.uk/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Acknowledgements S.H., S.S. and S.D. developed the study concept and gained funding for the work. S.H. developed the study design. J.B. and H.W. drafted the manuscript. J.B. and H.W. developed the coding frame and coded the articles. S.H., S.S. and S.D. critically revised the manuscript. Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was funded by Cancer Research UK (C47682/A16930) and the Scottish School of Public Health Research. Sheila Duffy is Chief Executive of ASH Scotland. Heide Weishaar and Shona Hilton are funded by the UK Medical Research Council as part of the Informing Healthly Public Policy programme (MC_UU12017-15) at the MRC/CSO Social and Public Health Sciences Unit, University of Glasgow. The authors declare no additional conflicting interest.