Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms (original) (raw)

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Acknowledgements

J.D. is a British Heart Foundation Professor, European Research Council Senior Investigator and NIHR Senior Investigator. J.D.E. and A.D.J. were supported by NHLBI Intramural Research Program funds. N.F. is supported by R21HL123677-01 and R56 DK104806-01A1. N.S. is supported by the British Heart Foundation and is an NIHR Senior Investigator. T.L.A. is supported by NIH career development award K23DK088942. This work was funded by the UK Medical Research Council (G0800270), the British Heart Foundation (SP/09/002), the UK National Institute for Health Research Cambridge Biomedical Research Centre, the European Research Council (268834), European Commission Framework Programme 7 (HEALTH-F2-2012-279233) and Pfizer. The eQTL database construction was supported by NHLBI intramural funds. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the US Department of Health and Human Services.

A full list of acknowledgments for the studies contributing to this work is provided in the Supplementary Note.

Author information

Author notes

1. Wei Zhao, Daniel R Barnes, Themistocles L Assimes, John Danesh, Adam S Butterworth and Danish Saleheen: These authors contributed equally to this work.

Authors and Affiliations

1. Department of Public Health and Primary Care, MRC/BHF Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, UK
   Joanna M M Howson, Daniel R Barnes, Weang-Kee Ho, Robin Young, Dirk S Paul, Daniel F Freitag, Benjamin B Sun, Wei-Yu Lin, Praveen Surendran, Emanuele Di Angelantonio, Rajiv Chowdhury, John Danesh, Adam S Butterworth & Danish Saleheen
2. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
   Wei Zhao & Danish Saleheen
3. Department of Applied Mathematics, University of Nottingham Malaysia Campus, Semenyih, Malaysia
   Weang-Kee Ho
4. Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
   Robin Young
5. HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA
   Lindsay L Waite & Devin Absher
6. Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA
   Eric B Fauman
7. Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, California, USA
   Elias L Salfati, Thomas Quertermous & Themistocles L Assimes
8. Stanford Cardiovascular Institute, Stanford University, Stanford, California, USA
   Elias L Salfati, Thomas Quertermous & Themistocles L Assimes
9. National Heart, Lung, and Blood Institute, Population Sciences Branch, Bethesda, Maryland, USA
   John D Eicher & Andrew D Johnson
10. NHLBI and Boston University's The Framingham Heart Study, Framingham, Massachusetts, USA
    John D Eicher & Andrew D Johnson
11. Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
    Wayne H H Sheu
12. School of Medicine, National Yang-Ming University, Taipei, Taiwan
    Wayne H H Sheu
13. College of Medicine, National Defense Medical Center, Taipei, Taiwan
    Wayne H H Sheu & Yi-Jen Hung
14. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
    Sune F Nielsen, Katrine L Rasmussen, Pia R Kamstrup & Børge G Nordestgaard
15. Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK
    Wei-Yu Lin
16. Pfizer Worldwide Research and Development, Stockholm, Sweden
    Anders Malarstig
17. Pfizer Worldwide Research and Development, Human Genetics, Cambridge, Massachusetts, USA
    Jemma B Wilk
18. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
    Anne Tybjærg-Hansen
19. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    Anne Tybjærg-Hansen & Børge G Nordestgaard
20. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
    Panos Deloukas
21. Centre for Genomic Health, Queen Mary University of London, London, UK
    Panos Deloukas
22. Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany
    Jeanette Erdmann
23. DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, Germany
    Jeanette Erdmann
24. University Heart Center Lübeck, Lübeck, Germany
    Jeanette Erdmann
25. Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
    Sekar Kathiresan
26. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    Sekar Kathiresan
27. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
    Nilesh J Samani
28. NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK
    Nilesh J Samani
29. Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
    Heribert Schunkert
30. DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
    Heribert Schunkert
31. Radcliffe Department of Medicine, University of Oxford, Oxford, UK
    Hugh Watkins
32. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
    Hugh Watkins
33. Department of Genetics and Genomic Sciences, Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
    Ron Do
34. Departments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Daniel J Rader
35. University of Florida College of Pharmacy, Gainesville, Florida, USA
    Julie A Johnson
36. Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland, Ohio, USA
    Stanley L Hazen
37. Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA
    Arshed A Quyyumi
38. Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA
    John A Spertus
39. Department of Biomedical and Health Informatics, University of Missouri–Kansas City, Kansas City, Missouri, USA
    John A Spertus
40. College of Medicine, University of Florida, Gainesville, Florida, USA
    Carl J Pepine
41. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA
    Nora Franceschini, Anne Justice, Kari E North, Kristin Young & Mariaelisa Graff
42. Department of Epidemiology, University of Washington, Seattle, Washington, USA
    Alex P Reiner
43. Department of Statistics and Biostatistics, Rutgers University, Piscataway, New Jersey, USA
    Steven Buyske
44. Division of Genomic Medicine, National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA
    Lucia A Hindorff
45. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
    Cara L Carty, Charles Kooperberg & Ulrike Peters
46. Carolina Center for Genome Sciences, Chapel Hill, North Carolina, USA
    Kari E North
47. Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA
    Eric Boerwinkle
48. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA
    Eric Boerwinkle
49. Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan
    Chao A Hsiung, Ying-Hsiang Chen & Ren-Hua Chung
50. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
    Wen-Jane Lee
51. Department of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA
    Kent D Taylor, Xiuqing Guo & Yii-Der Ida Chen
52. School of Medicine, Chung Shan Medical University, Taichung, Taiwan
    I-Te Lee
53. Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
    Yi-Jen Hung
54. Departments of Pediatrics and Medicine, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA
    Jerome I Rotter
55. Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
    Jyh-Ming J Juang & Tzung-Dau Wang
56. National Taiwan University College of Medicine, Taipei, Taiwan
    Jyh-Ming J Juang & Tzung-Dau Wang
57. Centre for Non-Communicable Disease, Karachi, Pakistan
    Asif Rasheed, Philippe Frossard & Danish Saleheen
58. School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada
    Dewan S Alam
59. National Institute of Cardiovascular Diseases, Sher-e-Bangla Nagar, Bangladesh
    Abdulla al Shafi Majumder
60. National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK
    Emanuele Di Angelantonio, John Danesh & Adam S Butterworth
61. Wellcome Trust Sanger Institute, Hinxton, UK
    John Danesh
62. Department of Medicine, British Heart Foundation Cambridge Centre of Excellence, University of Cambridge, Cambridge, UK
    John Danesh

Authors

1. Joanna M M Howson
2. Wei Zhao
3. Daniel R Barnes
4. Weang-Kee Ho
5. Robin Young
6. Dirk S Paul
7. Lindsay L Waite
8. Daniel F Freitag
9. Eric B Fauman
10. Elias L Salfati
11. Benjamin B Sun
12. John D Eicher
13. Andrew D Johnson
14. Wayne H H Sheu
15. Sune F Nielsen
16. Wei-Yu Lin
17. Praveen Surendran
18. Anders Malarstig
19. Jemma B Wilk
20. Anne Tybjærg-Hansen
21. Katrine L Rasmussen
22. Pia R Kamstrup
23. Panos Deloukas
24. Jeanette Erdmann
25. Sekar Kathiresan
26. Nilesh J Samani
27. Heribert Schunkert
28. Hugh Watkins
29. Ron Do
30. Daniel J Rader
31. Julie A Johnson
32. Stanley L Hazen
33. Arshed A Quyyumi
34. John A Spertus
35. Carl J Pepine
36. Nora Franceschini
37. Anne Justice
38. Alex P Reiner
39. Steven Buyske
40. Lucia A Hindorff
41. Cara L Carty
42. Kari E North
43. Charles Kooperberg
44. Eric Boerwinkle
45. Kristin Young
46. Mariaelisa Graff
47. Ulrike Peters
48. Devin Absher
49. Chao A Hsiung
50. Wen-Jane Lee
51. Kent D Taylor
52. Ying-Hsiang Chen
53. I-Te Lee
54. Xiuqing Guo
55. Ren-Hua Chung
56. Yi-Jen Hung
57. Jerome I Rotter
58. Jyh-Ming J Juang
59. Thomas Quertermous
60. Tzung-Dau Wang
61. Asif Rasheed
62. Philippe Frossard
63. Dewan S Alam
64. Abdulla al Shafi Majumder
65. Emanuele Di Angelantonio
66. Rajiv Chowdhury
67. Yii-Der Ida Chen
68. Børge G Nordestgaard
69. Themistocles L Assimes
70. John Danesh
71. Adam S Butterworth
72. Danish Saleheen

Consortia

CARDIoGRAMplusC4D

EPIC-CVD

Contributions

Central analysis group: J.M.M.H., W.Z., D.R.B., T.L.A., A.S.B., D.S. Writing group: J.M.M.H., W.Z., D.R.B., D.S.P., T.L.A., A.S.B., J.D. Study analysts: J.M.M.H., W.-K.H., R.Y., L.L.W., E.L.S., S.F.N., W.-Y.L., R.D., N.F., A.J., A.P.R., C.L.C., K.Y., M.G., D.A., C.A.H., Y.-H.C., X.G., T.L.A. Study PIs and co-PIs: W.H.-H.S., P.D., J.E., S.K., N.J.S., H.S., H.W., D.J.R., J.A.J., S.L.H., A.A.Q., J.S., C.J.P., K.E.N., C.K., U.P., C.A.H., W.-J.L., I.-T.L., R.-H.C., Y.-J.H., J.I.R., J.-M.J.J., T.Q., T.-D.W., D.S.A., A.a.S.M., E.D.A., R.C., Y.-D.I.C., B.G.N., T.L.A., J.D., A.S.B., D.S., A.R., P.F. Bioinformatics, eQTL, pQTL and pathway analyses: D.S.P., W.Z., D.R.B., D.F.F., T.L.A., E.B.F., A.M., J.B.W., E.L.S., B.B.S., A.S.B., J.D.E., A.D.J., P.S., T.L.A., J.M.M.H. Genotyping: S.B., L.A.H., C.K., E.B., U.P., D.A., K.D.T., T.Q., T.L.A. Phenotyping: W.H.H.S., A.T.-H., K.L.R., P.R.K., K.E.N., C.K., C.A.H., W.-J.L., I.-T.L., R.-H.C., Y.-J.H., J.-M.J.J., T.Q., Y.-D.I.C.

Corresponding author

Correspondence toJoanna M M Howson.

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Competing interests

A.M., E.B.F. and J.B.W. are full-time employees of Pfizer. D.F.F. is now a full-time employee of Bayer AG, Germany. J.D. reports personal fees and non-financial support from Merck Sharp & Dohme UK Atherosclerosis, the Novartis Cardiovascular & Metabolic Advisory Board, the Pfizer Population Research Advisory Panel and the Sanofi Advisory Board.

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A full list of members and affiliations appears in the Supplementary Note.

A full list of members and affiliations appears in the Supplementary Note.

Supplementary information

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Howson, J., Zhao, W., Barnes, D. et al. Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms.Nat Genet 49, 1113–1119 (2017). https://doi.org/10.1038/ng.3874

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• Received: 28 November 2016
• Accepted: 26 April 2017
• Published: 22 May 2017
• Issue date: 01 July 2017
• DOI: https://doi.org/10.1038/ng.3874