Background: Causal evidence of circulating lipids especially the remnant cholesterol with cardiovascular and cerebrovascular disease (CVD) is lacking. This research aimed to explore the causal roles of extensive lipid traits especially the remnant lipids in CVD. Methods: Two-sample Mendelian randomization (TSMR) analysis was performed based on large-scale meta-analysis datasets in European ancestry. The causal effect of 15 circulating lipid profiles including 6 conventional lipids and 9 remnant lipids on coronary heart disease (CHD) and ischemic stroke (IS), as well as the subtypes, was assessed. Results: Apolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were still important risk factors for CHD and myocardial infarction (MI) but not for IS. Apo B is the strongest which increased the CHD and MI risk by 44% and 41%, respectively. The odds ratios (ORs) of total TG on CHD and MI were 1.25 (95% confidence interval [CI], 1.13-1.38) and 1.24 (95% CI, 1.11-1.38), respectively. A one standard deviation difference increased TG in medium very-low-density lipoproteins (M.VLDL.TG), TG in small VLDL (S.VLDL.TG), TG in very small VLDL (XS.VLDL.TG), TG in intermediate-density lipoproteins (IDL.TG), TG in very large HDL (XL.HDL.TG), and TG in small HDL (S.HDL.TG) particles also robustly increased the risk of CHD and MI by 9-28% and 9-27%, respectively. TG in very= extremely large VLDL (XXL.VLDL.TG and XL.VLDL.TG) were insignificant or even negatively associated with CHD (in multivariable TSMR), and negatively associated with IS as well. Conclusion: The remnant lipids presented heterogeneity and two-sided effects for the risk of CHD and IS that may partially rely on the particle size. The findings suggested that the remnant lipids were required to be intervened according to specific components. This research confirms the importance of remnant lipids and provides causal evidence for potential targets for intervention.
机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Bulik-Sullivan, Brendan
;
Finucane, Hilary K.
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MIT, Dept Math, Cambridge, MA 02139 USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Finucane, Hilary K.
;
Anttila, Verneri
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h-index: 0
机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Anttila, Verneri
;
Gusev, Alexander
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Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Gusev, Alexander
;
Day, Felix R.
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Univ Cambridge, Sch Clin Med, Inst Metab Sci, Epidemiol Unit,MRC, Cambridge, EnglandBroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Day, Felix R.
;
Loh, Po-Ru
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机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Loh, Po-Ru
;
Duncan, Laramie
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Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Duncan, Laramie
;
Perry, John R. B.
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Univ Cambridge, Sch Clin Med, Inst Metab Sci, Epidemiol Unit,MRC, Cambridge, EnglandBroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Perry, John R. B.
;
Patterson, Nick
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Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Patterson, Nick
;
Robinson, Elise B.
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Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Robinson, Elise B.
;
Daly, Mark J.
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Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Daly, Mark J.
;
Price, Alkes L.
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机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Price, Alkes L.
;
Neale, Benjamin M.
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机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Bulik-Sullivan, Brendan
;
Finucane, Hilary K.
论文数: 0引用数: 0
h-index: 0
机构:
MIT, Dept Math, Cambridge, MA 02139 USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Finucane, Hilary K.
;
Anttila, Verneri
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h-index: 0
机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Anttila, Verneri
;
Gusev, Alexander
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机构:
Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Gusev, Alexander
;
Day, Felix R.
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h-index: 0
机构:
Univ Cambridge, Sch Clin Med, Inst Metab Sci, Epidemiol Unit,MRC, Cambridge, EnglandBroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Day, Felix R.
;
Loh, Po-Ru
论文数: 0引用数: 0
h-index: 0
机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Loh, Po-Ru
;
Duncan, Laramie
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机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Duncan, Laramie
;
Perry, John R. B.
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机构:
Univ Cambridge, Sch Clin Med, Inst Metab Sci, Epidemiol Unit,MRC, Cambridge, EnglandBroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Perry, John R. B.
;
Patterson, Nick
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h-index: 0
机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Patterson, Nick
;
Robinson, Elise B.
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h-index: 0
机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Robinson, Elise B.
;
Daly, Mark J.
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h-index: 0
机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Daly, Mark J.
;
Price, Alkes L.
论文数: 0引用数: 0
h-index: 0
机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Price, Alkes L.
;
Neale, Benjamin M.
论文数: 0引用数: 0
h-index: 0
机构:
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA
Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA USABroad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA