Display options
Cite
Blackburn NB, Meikle PJ, Peralta JM, et al. Identifying the Lipidomic Effects of a Rare Loss-of-Function Deletion in . Circ Genom Precis Med. 2021;14(3):e003232doi: 10.1161/CIRCGEN.120.003232.
Blackburn, N. B., Meikle, P. J., Peralta, J. M., Kumar, S., Leandro, A. C., Bellinger, M. A., Giles, C., Huynh, K., Mahaney, M. C., Göring, H. H. H., VandeBerg, J. L., Williams-Blangero, S., Glahn, D. C., Duggirala, R., Blangero, J., Michael, L. F., & Curran, J. E. (2021). Identifying the Lipidomic Effects of a Rare Loss-of-Function Deletion in . Circulation. Genomic and precision medicine, 14(3), e003232. https://doi.org/10.1161/CIRCGEN.120.003232
Blackburn, Nicholas B, et al. "Identifying the Lipidomic Effects of a Rare Loss-of-Function Deletion in ." Circulation. Genomic and precision medicine vol. 14,3 (2021): e003232. doi: https://doi.org/10.1161/CIRCGEN.120.003232
Blackburn NB, Meikle PJ, Peralta JM, Kumar S, Leandro AC, Bellinger MA, Giles C, Huynh K, Mahaney MC, Göring HHH, VandeBerg JL, Williams-Blangero S, Glahn DC, Duggirala R, Blangero J, Michael LF, Curran JE. Identifying the Lipidomic Effects of a Rare Loss-of-Function Deletion in . Circ Genom Precis Med. 2021 Jun;14(3):e003232. doi: 10.1161/CIRCGEN.120.003232. Epub 2021 Apr 22. PMID: 33887960; PMCID: PMC8206021.
Copy Download .nbib Format: NLM
Share it on

Circ Genom Precis Med. 2021 Jun;14(3):e003232. doi: 10.1161/CIRCGEN.120.003232. Epub 2021 Apr 22.

Identifying the Lipidomic Effects of a Rare Loss-of-Function Deletion in .

Circulation. Genomic and precision medicine

Nicholas B Blackburn, Peter J Meikle, Juan M Peralta, Satish Kumar, Ana C Leandro, Melissa A Bellinger, Corey Giles, Kevin Huynh, Michael C Mahaney, Harald H H Göring, John L VandeBerg, Sarah Williams-Blangero, David C Glahn, Ravindranath Duggirala, John Blangero, Laura F Michael, Joanne E Curran

Affiliations

  1. South Texas Diabetes and Obesity Institute (N.B.B., J.M.P., S.K., A.C.L., M.C.M., H.H.H.G., J.L.V., S.W.-B., R.D., J.B., J.E.C.), School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX.
  2. Department of Human Genetics (N.B.B., J.M.P., S.K., A.C.L., M.C.M., H.H.H.G., J.L.V., S.W.-B., R.D., J.B., J.E.C.), School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX.
  3. Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia (N.B.B., J.M.P.).
  4. Baker Heart and Diabetes Institute, Melbourne, VIC, Australia (P.J.M., C.G., K.H.).
  5. Eli Lilly and Company, Indianapolis, IN (M.A.B., L.F.M.).
  6. Department of Psychiatry, Boston Children's Hospital and Harvard Medical School, Boston, MA (D.C.G.).
  7. Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT (D.C.G.).

PMID: 33887960 PMCID: PMC8206021 DOI: 10.1161/CIRCGEN.120.003232

Abstract

BACKGROUND: The identification and understanding of therapeutic targets for atherosclerotic cardiovascular disease is of fundamental importance given its global health and economic burden. Inhibition of ANGPTL3 (angiopoietin-like 3) has demonstrated a cardioprotective effect, showing promise for atherosclerotic cardiovascular disease treatment, and is currently the focus of ongoing clinical trials. Here, we assessed the genetic basis of variation in ANGPTL3 levels in the San Antonio Family Heart Study.

METHODS: We assayed ANGPTL3 protein levels in ≈1000 Mexican Americans from extended pedigrees. By drawing upon existing plasma lipidome profiles and genomic data we conducted analyses to understand the genetic basis to variation in ANGPTL3 protein levels, and accordingly the correlation with the plasma lipidome.

RESULTS: In a variance components framework, we identified that variation in ANGPTL3 was significantly heritable (h

CONCLUSIONS: Variation in ANGPTL3 protein levels is heritable and under significant genetic control. Both ANGPTL3 levels and loss-of-function variants in

Keywords: association; cardiovascular diseases; genomic; lipidomic; pedigree; phenotype

References

  1. JAMA. 2009 Nov 11;302(18):1993-2000 - PubMed
  2. Am J Hum Genet. 1998 May;62(5):1198-211 - PubMed
  3. Circ Cardiovasc Genet. 2014 Dec;7(6):854-863 - PubMed
  4. J Am Coll Cardiol. 2017 Apr 25;69(16):2054-2063 - PubMed
  5. IUBMB Life. 2014 Sep;66(9):616-23 - PubMed
  6. BMC Proc. 2018 Sep 17;12(Suppl 9):52 - PubMed
  7. N Engl J Med. 2020 Aug 20;383(8):711-720 - PubMed
  8. J Lipid Res. 2013 Jul;54(7):1939-48 - PubMed
  9. JCI Insight. 2019 Jul 11;4(13): - PubMed
  10. Arterioscler Thromb Vasc Biol. 2014 May;34(5):1057-63 - PubMed
  11. Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):805-9 - PubMed
  12. J Clin Invest. 2009 Jan;119(1):70-9 - PubMed
  13. Circ Res. 2020 Sep 25;127(8):1112-1114 - PubMed
  14. Cancer Res. 2017 Nov 1;77(21):e31-e34 - PubMed
  15. J Lipid Res. 2020 Sep;61(9):1271-1286 - PubMed
  16. N Engl J Med. 2017 Jul 20;377(3):211-221 - PubMed
  17. BMC Med Genet. 2007 Sep 19;8 Suppl 1:S17 - PubMed
  18. Am J Med Genet B Neuropsychiatr Genet. 2011 Jul;156B(5):561-8 - PubMed
  19. Nature. 2020 May;581(7809):434-443 - PubMed
  20. N Engl J Med. 2020 Dec 10;383(24):2307-2319 - PubMed
  21. J Biol Chem. 2002 Sep 13;277(37):33742-8 - PubMed
  22. Gigascience. 2015 Feb 25;4:7 - PubMed
  23. Clin Chim Acta. 2012 Mar 22;413(5-6):552-5 - PubMed
  24. J Lipid Res. 2013 Oct;54(10):2898-908 - PubMed
  25. Clin Gastroenterol Hepatol. 2020 Aug 12;: - PubMed
  26. Heredity (Edinb). 2005 Sep;95(3):221-7 - PubMed
  27. Arterioscler Thromb Vasc Biol. 2000 May;20(5):1309-15 - PubMed
  28. J Med Genet. 2012 Jul;49(7):433-6 - PubMed
  29. Arterioscler Thromb Vasc Biol. 2013 Jul;33(7):1706-13 - PubMed
  30. Eur Heart J. 2020 Oct 21;41(40):3936-3945 - PubMed
  31. N Engl J Med. 2017 Jul 20;377(3):296-297 - PubMed
  32. Circulation. 2017 Jul 18;136(3):e1-e23 - PubMed
  33. J Hum Genet. 2011 Jun;56(6):428-35 - PubMed
  34. Genet Epidemiol. 2011 Sep;35(6):557-67 - PubMed
  35. Sci Rep. 2017 Oct 2;7(1):12485 - PubMed
  36. N Engl J Med. 2010 Dec 2;363(23):2220-7 - PubMed
  37. Nat Genet. 2002 Feb;30(2):151-7 - PubMed
  38. Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):366-72 - PubMed
  39. Circulation. 1996 Nov 1;94(9):2159-70 - PubMed
  40. Nat Genet. 2008 Feb;40(2):189-97 - PubMed
  41. Genome Res. 2009 Sep;19(9):1655-64 - PubMed
  42. Nat Commun. 2018 Aug 23;9(1):3391 - PubMed
  43. N Engl J Med. 2017 Jul 20;377(3):222-232 - PubMed
  44. J Lipid Res. 2019 Sep;60(9):1630-1639 - PubMed
  45. Nature. 2021 Feb;590(7845):290-299 - PubMed
  46. Nat Genet. 2008 Feb;40(2):161-9 - PubMed
  47. Front Cell Dev Biol. 2020 Dec 14;8:595849 - PubMed
  48. Circ Cardiovasc Genet. 2012 Feb 1;5(1):42-50 - PubMed
  49. Neuropsychopharmacology. 2018 Dec;43(13):2556-2563 - PubMed

Publication Types

Grant support