Common variants associated with plasma triglycerides and risk for coronary artery disease
- PMID: 24097064
- PMCID: PMC3904346
- DOI: 10.1038/ng.2795
Common variants associated with plasma triglycerides and risk for coronary artery disease
Abstract
Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
Figures
Similar articles
-
Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions.PLoS One. 2014 Oct 10;9(10):e108891. doi: 10.1371/journal.pone.0108891. eCollection 2014. PLoS One. 2014. PMID: 25302496 Free PMC article.
-
Genetic variants influencing circulating lipid levels and risk of coronary artery disease.Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2264-76. doi: 10.1161/ATVBAHA.109.201020. Epub 2010 Sep 23. Arterioscler Thromb Vasc Biol. 2010. PMID: 20864672 Free PMC article.
-
Genetics of lipid traits and relationship to coronary artery disease.Curr Cardiol Rep. 2013 Sep;15(9):396. doi: 10.1007/s11886-013-0396-9. Curr Cardiol Rep. 2013. PMID: 23881580 Free PMC article. Review.
-
Newly identified loci that influence lipid concentrations and risk of coronary artery disease.Nat Genet. 2008 Feb;40(2):161-9. doi: 10.1038/ng.76. Epub 2008 Jan 13. Nat Genet. 2008. PMID: 18193043 Free PMC article.
-
Surprises From Genetic Analyses of Lipid Risk Factors for Atherosclerosis.Circ Res. 2016 Feb 19;118(4):579-85. doi: 10.1161/CIRCRESAHA.115.306398. Circ Res. 2016. PMID: 26892959 Free PMC article. Review.
Cited by
-
Lessons from PROMINENT and prospects for pemafibrate.Cardiovasc Diabetol. 2024 Jul 29;23(1):279. doi: 10.1186/s12933-024-02305-z. Cardiovasc Diabetol. 2024. PMID: 39080716
-
Fenofibrate's impact on cardiovascular risk in patients with diabetes: a nationwide propensity-score matched cohort study.Cardiovasc Diabetol. 2024 Jul 18;23(1):263. doi: 10.1186/s12933-024-02353-5. Cardiovasc Diabetol. 2024. PMID: 39026240 Free PMC article.
-
Effects of genetically proxied lipid-lowering drugs on acute myocardial infarction: a drug-target mendelian randomization study.Lipids Health Dis. 2024 Jun 3;23(1):163. doi: 10.1186/s12944-024-02133-w. Lipids Health Dis. 2024. PMID: 38831433 Free PMC article.
-
Association between basal metabolic rate and cardio-metabolic risk factors: Evidence from a Mendelian Randomization study.Heliyon. 2024 Mar 23;10(7):e28154. doi: 10.1016/j.heliyon.2024.e28154. eCollection 2024 Apr 15. Heliyon. 2024. PMID: 38590845 Free PMC article.
-
Pleiotropy, epistasis and the genetic architecture of quantitative traits.Nat Rev Genet. 2024 Apr 2. doi: 10.1038/s41576-024-00711-3. Online ahead of print. Nat Rev Genet. 2024. PMID: 38565962 Review.
References
-
- Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet. 1997;349:1436–42. - PubMed
-
- Sarwar N, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007;115:450–8. - PubMed
-
- Davey Smith G, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32:1–22. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- PG/08/094/26019/BHF_/British Heart Foundation/United Kingdom
- G0901213/MRC_/Medical Research Council/United Kingdom
- RG/08/008/25291/BHF_/British Heart Foundation/United Kingdom
- R01HL107816/HL/NHLBI NIH HHS/United States
- T32 HG000040/HG/NHGRI NIH HHS/United States
- UL1 TR000124/TR/NCATS NIH HHS/United States
- T32 HL007208/HL/NHLBI NIH HHS/United States
- P30 DK063491/DK/NIDDK NIH HHS/United States
- G0401527/MRC_/Medical Research Council/United Kingdom
- G0701863/MRC_/Medical Research Council/United Kingdom
- T32HL007208/HL/NHLBI NIH HHS/United States
- R01 DK093757/DK/NIDDK NIH HHS/United States
- MR/K013351/1/MRC_/Medical Research Council/United Kingdom
- CZB/4/672/CSO_/Chief Scientist Office/United Kingdom
- CZB/4/710/CSO_/Chief Scientist Office/United Kingdom
- R01 HL107816/HL/NHLBI NIH HHS/United States
- R01 HL109946/HL/NHLBI NIH HHS/United States
- MR/L003120/1/MRC_/Medical Research Council/United Kingdom
- MC_U123092720/MRC_/Medical Research Council/United Kingdom
- MC_U950080926/MRC_/Medical Research Council/United Kingdom
- R01 DK072193/DK/NIDDK NIH HHS/United States
- CAPMC/ CIHR/Canada
- R01 HL105756/HL/NHLBI NIH HHS/United States
- G0801566/MRC_/Medical Research Council/United Kingdom
- 100891/WT_/Wellcome Trust/United Kingdom
- RG/08/014/24067/BHF_/British Heart Foundation/United Kingdom
- MC_U106179472/MRC_/Medical Research Council/United Kingdom
- G1000143/MRC_/Medical Research Council/United Kingdom
- 090532/WT_/Wellcome Trust/United Kingdom
- MC_PC_U127561128/MRC_/Medical Research Council/United Kingdom
- P30 DK020572/DK/NIDDK NIH HHS/United States
- MR/K013491/1/MRC_/Medical Research Council/United Kingdom
- MC_U106179471/MRC_/Medical Research Council/United Kingdom
- MC_U106188470/MRC_/Medical Research Council/United Kingdom
- U01 HL069757/HL/NHLBI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous