Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program (original) (raw)

Data availability

The full summary-level association data from the trans-ancestry meta-analysis for each lipid trait from this report are available through dbGaP, with accession number phs001672.v1.p1.

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Acknowledgements

Data on patients with coronary artery disease and myocardial infarctions have been contributed by the CARDIoGRAMplusC4D investigators and the Myocardial Infarction Genetics and CARDIoGRAM Exome investigators. Both datasets were obtained online (see URLs). This research is based on data from the MVP, Office of Research and Development, Veterans Health Administration, and was supported by the Department of Veterans Affairs Cooperative Studies Program award G002. This research was also supported by three additional Department of Veterans Affairs awards (1I0101BX003340, 1I01BX003362, and 1I01CX001025) and the NIH (T32 HL007734, K01HL125751, R01HL127564). The content of this manuscript does not represent the views of the Department of Veterans Affairs or the United States Government.

Author information

Author notes

  1. These authors contributed equally: Derek Klarin, Scott M. Damrauer.
  2. These authors jointly supervised: Christopher J. O’Donnell, Philip S. Tsao, Sekar Kathiresan, Daniel J. Rader, Peter W. F. Wilson, Themistocles L. Assimes.
  3. A list of members and affiliations appears in the Supplementary Note.

Authors and Affiliations

  1. Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Derek Klarin, Connor A. Emdin, Pradeep Natarajan, Amit V. Khera & Sekar Kathiresan
  2. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
    Derek Klarin, Mark Chaffin, Connor A. Emdin, Pradeep Natarajan, Benjamin M. Neale, Amit V. Khera & Sekar Kathiresan
  3. Boston VA Healthcare System, Boston, MA, USA
    Derek Klarin
  4. Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, USA
    Scott M. Damrauer, Aeron M. Small, Danish Saleheen, Marijana Vujkovic & Kyong-Mi Chang
  5. Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Scott M. Damrauer
  6. Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA
    Kelly Cho, Jacqueline Honerlaw, David R. Gagnon, Jie Huang, Yuk-Lam Ho, Jennifer E. Huffman, Saiju Pyarajan, J. Michael Gaziano & Christopher J. O’Donnell
  7. Department of Epidemiology, Rollins School of Public Health, Department of Biomedical Informatics, School of Medicine, Emory University, Atlanta, GA, USA
    Yan V. Sun
  8. Regeneron Genetics Center, Tarrytown, NY, USA
    Tanya M. Teslovich, Alexander H. Li, Aris Baras & Frederick E. Dewey
  9. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
    David R. Gagnon & Gina M. Peloso
  10. VA Salt Lake City Health Care System, Salt Lake City, UT, USA
    Scott L. DuVall & Julie A. Lynch
  11. Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
    Scott L. DuVall
  12. Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
    Jin Li, Jennifer S. Lee, Philip S. Tsao & Themistocles L. Assimes
  13. VA Palo Alto Health Care System, Palo Alto, CA, USA
    Jin Li, Jennifer S. Lee, Philip S. Tsao & Themistocles L. Assimes
  14. Department of Medicine, Yale School of Medicine, New Haven, CT, USA
    Aeron M. Small & John Concato
  15. Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA
    Hua Tang
  16. University of Massachusetts College of Nursing and Health Sciences, Boston, MA, USA
    Julie A. Lynch
  17. Department of Public Health Sciences, Institute of Personalized Medicine, Penn State College of Medicine, Hershey, PA, USA
    Dajiang J. Liu
  18. Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Pradeep Natarajan
  19. Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
    Rajiv Chowdhury, Emanuele Di Angelantonio & John Danesh
  20. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Danish Saleheen & Marijana Vujkovic
  21. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
    Saiju Pyarajan & J. Michael Gaziano
  22. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
    Benjamin M. Neale
  23. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
    Benjamin M. Neale
  24. Initiative for Noncommunicable Diseases, Health Systems and Population Studies Division, International Centre for Diarrheal Disease Research, Dhaka, Bangladesh
    Aliya Naheed
  25. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Kyong-Mi Chang & Daniel J. Rader
  26. Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
    Gonçalo Abecasis
  27. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA
    Cristen Willer
  28. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA
    Cristen Willer
  29. Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
    Cristen Willer
  30. Geisinger Health System, Danville, PA, USA
    David J. Carey
  31. Clinical Epidemiology Research Center, VA Connecticut Healthcare System, West Haven, CT, USA
    John Concato
  32. Department of Medicine, Harvard Medical School, Boston, MA, USA
    J. Michael Gaziano, Christopher J. O’Donnell & Daniel J. Rader
  33. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Daniel J. Rader
  34. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Daniel J. Rader
  35. Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Daniel J. Rader
  36. Atlanta VA Medical Center, Decatur, GA, USA
    Peter W. F. Wilson
  37. Emory Clinical Cardiovascular Research Institute, Atlanta, GA, USA
    Peter W. F. Wilson

Authors

  1. Derek Klarin
  2. Scott M. Damrauer
  3. Kelly Cho
  4. Yan V. Sun
  5. Tanya M. Teslovich
  6. Jacqueline Honerlaw
  7. David R. Gagnon
  8. Scott L. DuVall
  9. Jin Li
  10. Gina M. Peloso
  11. Mark Chaffin
  12. Aeron M. Small
  13. Jie Huang
  14. Hua Tang
  15. Julie A. Lynch
  16. Yuk-Lam Ho
  17. Dajiang J. Liu
  18. Connor A. Emdin
  19. Alexander H. Li
  20. Jennifer E. Huffman
  21. Jennifer S. Lee
  22. Pradeep Natarajan
  23. Rajiv Chowdhury
  24. Danish Saleheen
  25. Marijana Vujkovic
  26. Aris Baras
  27. Saiju Pyarajan
  28. Emanuele Di Angelantonio
  29. Benjamin M. Neale
  30. Aliya Naheed
  31. Amit V. Khera
  32. John Danesh
  33. Kyong-Mi Chang
  34. Gonçalo Abecasis
  35. Cristen Willer
  36. Frederick E. Dewey
  37. David J. Carey
  38. John Concato
  39. J. Michael Gaziano
  40. Christopher J. O’Donnell
  41. Philip S. Tsao
  42. Sekar Kathiresan
  43. Daniel J. Rader
  44. Peter W. F. Wilson
  45. Themistocles L. Assimes

Consortia

Global Lipids Genetics Consortium

Myocardial Infarction Genetics (MIGen) Consortium

The Geisinger-Regeneron DiscovEHR Collaboration

The VA Million Veteran Program

Contributions

Concept and design: D.K., T.L.A., S.M.D., K.C., K.-M.C., P.S.T., S.K., D.J.R., P.W.F.W., J.C. and J.M.G. Acquisition, analysis or interpretation of data: D.K., S.M.D., Y.V.S., K.C., T.M.T., J.Ho., D.R.G., S.L.D., J.L., G.M.P., M.C., A.M.S., J.Hu., H.T., J.S.L., Y.-L.H., D.J.L., C.A.E., A.H.L., J.A.L., R.C., P.N., D.S., M.V., A.B., S.P., E.D.A., B.M.N., A.N., A.V.K., J.D., K.-M.C., G.A., C.W., F.E.D., J.E.H. and D.J.C. Drafting of the manuscript: D.K. and T.L.A. Critical revision of the manuscript for important intellectual content: S.M.D., Y.V.S., K.C., P.N., C.W., J.A.L., F.E.D., S.L.D., K.-M.C., C.J.O., P.S.T., S.K., D.J.R. and P.W.W. Administrative, technical or material support: D.K., Y.V.S., K.C., J.Ho., D.R.G., S.L.D., J.A.L., Y.H., J.C., J.M.G., C.J.O., P.S.T, J.E.H., and P.W.W.

Corresponding author

Correspondence toThemistocles L. Assimes.

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Competing interests

S.K. reports grant support from Regeneron and Bayer, grant support and personal fees from Aegerion, personal fees from Regeneron Genetics Center, Merck, Celera, Novartis, Bristol-Myers Squibb, Sanofi, AstraZeneca, Alnylam, Eli Lilly and Leerink Partners, personal fees and other support from Catabasis, and other support from San Therapeutics outside the submitted work. He is also the chair of the scientific advisory board at Genomics Plc. T.M.T., A.H.L., A.B., F.E.D. and D.J.C. are employees of Regeneron Pharmaceuticals. G.A. has received consulting income from Regeneron Genetics Center, 23andMe and Helix. S.L.D. has received research grant support from the following for-profit companies through the University of Utah or the Western Institute for Biomedical Research (VA Salt Lake City’s affiliated non-profit): AbbVie Inc., Anolinx LLC, Astellas Pharma Inc., AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim International GmbH, Celgene Corporation, Eli Lilly and Company, Genentech Inc., Genomic Health Inc., Gilead Sciences Inc., GlaxoSmithKline PLC, Innocrin Pharmaceuticals Inc., Janssen Pharmaceuticals Inc., Kantar Health, Myriad Genetic Laboratories Inc., Novartis International AG and PAREXEL International Corporation.

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Klarin, D., Damrauer, S.M., Cho, K. et al. Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.Nat Genet 50, 1514–1523 (2018). https://doi.org/10.1038/s41588-018-0222-9

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