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Nutr Diabetes. 2014 Jun 16;4:e118. doi: 10.1038/nutd.2014.16.

Genetic risk score and adiposity interact to influence triglyceride levels in a cohort of Filipino women.

Nutrition & diabetes

N Zubair, E J Mayer-Davis, M A Mendez, K L Mohlke, K E North, L S Adair

Affiliations

  1. Public Health Sciences Division, Cancer Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  2. Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  3. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  4. Department of Epidemiology and Carolina Center for Genome Sciences, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

PMID: 24932782 PMCID: PMC4079926 DOI: 10.1038/nutd.2014.16

Abstract

BACKGROUND/OBJECTIVES: Individually, genetic variants only moderately influence cardiometabolic (CM) traits, such as lipid and inflammatory markers. In this study we generated genetic risk scores from a combination of previously reported variants influencing CM traits, and used these scores to explore how adiposity levels could mediate genetic contributions to CM traits.

SUBJECTS/METHODS: Participants included 1649 women from the 2005 Cebu Longitudinal Health and Nutrition Survey. Three genetic risk scores were constructed for C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs). We used linear regression models to assess the association between each genetic risk score and its related trait. We also tested for interactions between each score and measures of adiposity.

RESULTS: Each genetic risk score explained a greater proportion of variance in trait levels than any individual genetic variant. We found an interaction between the TG genetic risk score (2.29-14.34 risk alleles) and waist circumference (WC) (Pinteraction=1.66 × 10(-2)). Based on model predictions, for individuals with a higher TG genetic risk score (75th percentile=12), having an elevated WC (⩾80 cm) increased TG levels from 1.32 to 1.71 mmol l(-1). However, for individuals with a lower score (25th percentile=7), having an elevated WC did not significantly change TG levels.

CONCLUSIONS: The TG genetic risk score interacted with adiposity to synergistically influence TG levels. For individuals with a genetic predisposition to elevated TG levels, our results suggest that reducing adiposity could possibly prevent further increases in TG levels and thereby lessen the likelihood of adverse health outcomes such as cardiovascular disease.

References

  1. Hum Mol Genet. 2010 May 15;19(10):2050-8 - PubMed
  2. Diabetes. 2005 Feb;54(2):333-9 - PubMed
  3. Ann Epidemiol. 2008 Oct;18(10):760-7 - PubMed
  4. JAMA. 2010 Feb 17;303(7):631-7 - PubMed
  5. Obes Res. 2004 Aug;12(8):1335-41 - PubMed
  6. J Nutr. 2008 Dec;138(12):2442-7 - PubMed
  7. J Hum Genet. 2011 Dec;56(12):823-7 - PubMed
  8. Lancet. 2005 Nov 5;366(9497):1640-9 - PubMed
  9. Asia Pac J Clin Nutr. 2012;21(2):271-81 - PubMed
  10. Inflammation. 2012 Apr;35(2):574-83 - PubMed
  11. Int J Epidemiol. 2011 Jun;40(3):619-25 - PubMed
  12. Nat Genet. 2009 Jan;41(1):5-6 - PubMed
  13. Lancet. 2004 Jan 10;363(9403):157-63 - PubMed
  14. Nat Genet. 2011 Sep 11;43(10):990-5 - PubMed
  15. Atherosclerosis. 2000 May;150(1):135-41 - PubMed
  16. Circulation. 2002 Dec 17;106(25):3143-421 - PubMed
  17. Lancet. 2005 Sep 24-30;366(9491):1059-62 - PubMed
  18. Nutr Rev. 2012 Jan;70(1):3-21 - PubMed
  19. Diabetes Care. 2004 Jan;27(1):283-4 - PubMed
  20. Lancet. 2010 Oct 23;376(9750):1393-400 - PubMed
  21. Lancet. 1991 Feb 16;337(8738):382-6 - PubMed
  22. Genet Epidemiol. 2010 Dec;34(8):816-34 - PubMed
  23. Nutrition. 2000 Jul-Aug;16(7-8):486-7 - PubMed
  24. Lancet. 2012 Dec 15;380(9859):2224-60 - PubMed
  25. Asia Pac J Clin Nutr. 2011;20(2):190-5 - PubMed
  26. Diabetes Care. 2009 Oct;32(10):1916-20 - PubMed
  27. Am J Hum Genet. 2008 May;82(5):1185-92 - PubMed
  28. J Lipid Res. 2013 Nov;54(11):3198-205 - PubMed
  29. PLoS Genet. 2011 Oct;7(10):e1002333 - PubMed
  30. Circulation. 2000 Jul 11;102(2):179-84 - PubMed
  31. Obes Rev. 2002 Aug;3(3):209-15 - PubMed
  32. Am J Clin Nutr. 1994 Jul;60(1):23-8 - PubMed
  33. Nature. 2010 Aug 5;466(7307):707-13 - PubMed
  34. Diabetologia. 2009 Dec;52(12):2578-84 - PubMed
  35. J Clin Endocrinol Metab. 2011 Jul;96(7):E1142-7 - PubMed
  36. Circulation. 2003 Jan 28;107(3):499-511 - PubMed
  37. Circulation. 2005 Apr 19;111(15):1883-90 - PubMed
  38. Am J Clin Nutr. 2012 Oct;96(4):714-26 - PubMed
  39. J Korean Med Sci. 2004 Apr;19(2):195-201 - PubMed
  40. JAMA. 1998 Dec 2;280(21):1843-8 - PubMed
  41. Am J Hum Genet. 2007 Sep;81(3):559-75 - PubMed
  42. Circulation. 2007 Jul 3;116(1):39-48 - PubMed
  43. Circulation. 2011 Feb 22;123(7):731-8 - PubMed
  44. Nat Genet. 2009 Jan;41(1):47-55 - PubMed
  45. Nat Genet. 2006 Aug;38(8):904-9 - PubMed
  46. Int J Obes (Lond). 2009 Feb;33(2):267-72 - PubMed
  47. Atherosclerosis. 2012 Dec;225(2):363-9 - PubMed

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