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A Mendelian randomization study of the role of lipoprotein subfractions in coronary artery disease

  1. Qingyuan Zhao  Is a corresponding author
  2. Jingshu Wang
  3. Zhen Miao
  4. Nancy R Zhang
  5. Sean Hennessy
  6. Dylan S Small
  7. Daniel J Rader
  1. Statistical Laboratory, University of Cambridge, United Kingdom
  2. Department of Statistics, University of Chicago, United States
  3. Perelman School of Medicine, University of Pennsylvania, United States
  4. Department of Statistics, University of Pennsylvania, United States
  5. Department of Medicine, University of Pennsylvania, United States
Research Article
Cite this article as: eLife 2021;10:e58361 doi: 10.7554/eLife.58361
11 figures, 15 tables and 1 additional file

Figures

Genetic correlation matrix of the 27 lipoprotein subfraction traits selected in phenotypic screening and five traditional lipid traits.

White asterisk indicates the correlation is statistically significant after Bonferroni correction for multiple comparisons at level 0.05.

Results of the Mendelian randomization analyses (false discover rate = 0.05): Estimated odds ratio [95% confidence interval] per standard deviation increase of the selected lipoprotein measurements on MI or CAD.
Genetic markers for HDL size (with risk alleles) and their associations with various lipid traits.
Appendix 2—figure 1
Genetic correlations computed using the Davis et al., 2017 GWAS summary dataset.
Appendix 2—figure 2
Genetic correlations computed using the Kettunen et al., 2016 GWAS summary dataset.
Appendix 2—figure 3
Genetic correlations computed by meta-analyzing the results in Appendix 2—figures 1 and 2.
Appendix 3—figure 1
Mendelian randomization results for the 27 lipoprotein measurements selected in phenotypic screening.
Appendix 4—figure 1
Diagnostic plots for S-HDL-P (selection: Davis; exposure: Kettunen; outcome: UK Biobank).
Appendix 4—figure 2
Diagnostic plots for M-HDL-P (selection: Davis; exposure: Kettunen; outcome: UK Biobank).
Appendix 4—figure 3
Scatter-plots for S-HDL-P with the effects on CAD adjusted for LDL-C and TG.

Red lines correspond the fitted effects of S-HDL-P in multivariable MR.

Appendix 4—figure 4
Scatter-plots for M-HDL-P with the effects on CAD adjusted for LDL-C and TG.

Red lines correspond the fitted effects of M-HDL-P in multivariable MR.

Tables

Table 1
Information about the GWAS summary datasets used in this article.

The columns are the phenotypes reported by the GWAS studies, the consortium or name of the first author of the publication, PubMed ID, population, sample size, other GWAS datasets with other lapping sample, and URLs we used to download the datasets.

PhenotypeDataset namePubMed IDPopulationSample sizeSample overlap with other datasetsURL to summary dataset
Traditional lipid traitsGERA29507422 Hoffmann et al., 2018Multi-ethnic94,674ftp://ftp.ebi.ac.uk/pub/databases/gwas/summary_statistics/
GLGC24097068 Willer et al., 2013European188,578Kettunen, CARDIoGRAMplusC4Dhttp://csg.sph.umich.edu/abecasis/public/lipids2013/
Lipoprotein subfraction traitsDavis29084231 Davis et al., 2017Finnish8372http://csg.sph.umich.edu/boehnke/public/metsim-2017-lipoproteins/
Kettunen27005778 Kettunen et al., 2016European24,925GLGC, CARDIoGRAMplusC4Dhttp://www.computationalmedicine.fi/data#NMR_GWAS
Heart disease traitsCARDIoGRAMplusC4D (CAD)26343387 Nikpay et al., 2015Mostly European185,000GLGC, Kettunenhttp://www.cardiogramplusc4d.org/data-downloads/
CARDIoGRAMplusC4D + UK Biobank (CAD)28714975 Nelson et al., 2017Mostly European
UK Biobank (MI)Interim round two release Abbott et al., 2018European360,420http://www.nealelab.is/uk-biobank/
Table 2
Results of some multivariable Mendelian randomization analyses.

Each row in the table corresponds to a multivariable MR analysis with traditional lipid profile and the specified lipoprotein subfraction or particle size trait. Reported numbers are the point estimates and 95% confidence intervals of the exposure effect.

TraitEffect of TGEffect of LDL-CEffect of HDL-CEffect of subfraction/particle size
None0.19 [0.09,0.29]0.38 [0.33,0.44]−0.053 [-0.13,0.03]
M-HDL-P0.37 [0.22,0.52]0.39 [0.32,0.45]0.30 [0.08,0.52]−0.69 [-1.09,–0.3]
S-HDL-P0.23 [0.12,0.33]0.45 [0.38,0.52]−0.11 [-0.2,–0.02]−0.33 [-0.52,–0.15]
HDL-D0.11 [0.00,0.22]0.42 [0.36,0.49]−0.44 [-0.69,–0.2]0.33 [0.11,0.56]
Effect of TGEffect of ApoBEffect of ApoA1Effect of Subfraction/Particle size
None0.05 [-0.05,0.14]0.49 [0.38,0.60]−0.095 [-0.21,0.02]
M-HDL-P−0.00 [-0.18,0.17]0.50 [0.31,0.69]0.13 [-0.06,0.32]−0.47 [-0.80,–0.15]
S-HDL-P0.07 [-0.03,0.17]0.53 [0.41,0.65]−0.13 [-0.25,–0.02]−0.24 [-0.40,–0.08]
HDL-D0.06 [-0.04,0.15]0.61 [0.47,0.76]−0.46 [-0.73,–0.19]0.30 [0.08,0.52]
Appendix 1—table 1
All 82 traits included in this study and whether they are measured in the Kettunen and Davis GWAS (NA means not available).
TraitDescriptionKettunenDavis
VLDL traits and total triglycerides
TGTotal triglycerides
VLDL-DVLDL diameter
XS-VLDL-LTotal lipids in very small VLDLNA
XS-VLDL-PConcentration of very small VLDL particles
XS-VLDL-PLPhospholipids in very small VLDL
XS-VLDL-TGTriglycerides in very small VLDL
S-VLDL-CTotal cholesterol in small VLDL
S-VLDL-FCFree cholesterol in small VLDL
S-VLDL-LTotal lipids in small VLDLNA
S-VLDL-PConcentration of small VLDL particles
S-VLDL-PLPhospholipids in small VLDL
S-VLDL-TGTriglycerides in small VLDL
M-VLDL-CTotal cholesterol in medium VLDL
M-VLDL-CECholesterol esters in medium VLDL
M-VLDL-FCFree cholesterol in medium VLDL
M-VLDL-LTotal lipids in medium VLDLNA
M-VLDL-PConcentration of medium VLDL particles
M-VLDL-PLPhospholipids in medium VLDL
M-VLDL-TGTriglycerides in medium VLDL
L-VLDL-CTotal cholesterol in large VLDL
L-VLDL-CECholesterol esters in large VLDL
L-VLDL-FCFree cholesterol in large VLDL
L-VLDL-LTotal lipids in large VLDLNA
L-VLDL-PConcentration of large VLDL particles
L-VLDL-PLPhospholipids in large VLDL
L-VLDL-TGTriglycerides in large VLDL
XL-VLDL-LTotal lipids in very large VLDLNA
XL-VLDL-PConcentration of very large VLDL particles
XL-VLDL-PLPhospholipids in very large VLDL
XL-VLDL-TGTriglycerides in very large VLDL
XXL-VLDL-LTotal lipids in chylomicrons and extremely very large VLDLNA
XXL-VLDL-PConcentration of chylomicrons and extremely very large VLDL particles
XXL-VLDL-PLPhospholipids in chylomicrons and extremely very large
XXL-VLDL-TGTriglycerides in chylomicrons and extremely very large
LDL and IDL traits
LDL-CTotal cholesterol in LDL
ApoBApolipoprotein B
LDL-DLDL diameter
S-LDL-CTotal cholesterol in small LDL
S-LDL-LTotal lipids in small LDLNA
S-LDL-PPhospholipids in small LDL
M-LDL-CTotal cholesterol in medium LDL
M-LDL-CECholesterol esters in medium LDL
M-LDL-LTotal lipids in medium LDLNA
M-LDL-PConcentration of medium LDL particles
M-LDL-PLPhospholipids in medium LDL
L-LDL-CTotal cholesterol in large LDL
L-LDL-CECholesterol esters in large LDL
L-LDL-FCFree cholesterol in large LDL
L-LDL-LTotal lipids in large LDLNA
L-LDL-PConcentration of large LDL particles
L-LDL-PLPhospholipids in large LDL
IDL-CTotal cholesterol in IDL
IDL-FCFree cholesterol in IDL
IDL-LTotal lipids in IDLNA
IDL-PConcentration of IDL particles
IDL-PLPhospholipids in IDL
IDL-TGTriglycerides in IDL
HDL traits
HDL-CTotal cholesterol in HDL
ApoA1Apolipoprotein A1
HDL-DHDL diameter
S-HDL-LTotal lipids in small HDLNA
S-HDL-PConcentration of small HDL particles
S-HDL-TGTriglycerides in small HDL
M-HDL-CTotal cholesterol in medium HDL
M-HDL-CECholesterol esters in medium HDL
M-HDL-FCFree cholesterol in medium HDL
M-HDL-LTotal lipids in medium HDLNA
M-HDL-PConcentration of medium HDL particles
M-HDL-PLPhospholipids in medium HDL
L-HDL-CTotal cholesterol in large HDL
L-HDL-CECholesterol esters in large HDL
L-HDL-FCFree cholesterol in large HDL
L-HDL-LTotal lipids in large HDLNA
L-HDL-PConcentration of large HDL particles
L-HDL-PLPhospholipids in large HDL
XL-HDL-CTotal cholesterol in very large HDL
XL-HDL-CECholesterol esters in very large HDL
XL-HDL-FCFree cholesterol in very large HDL
XL-HDL-LTotal lipids in very large HDLNA
XL-HDL-PConcentration of very large HDL particles
XL-HDL-PLPhospholipids in very large HDL
XL-HDL-TGTriglycerides in very large HDL
Appendix 2—table 1
Estimated genetic correlation (standard error) of the lipoprotein subfractions with the traditional lipid risk factors using the Davis GWAS.

Bolded estimates are above 0.8 and the corresponding traits were removed in phenotypic screening.

TraitApoA1ApoBHDL-CLDL-CTG
S-HDL-L0.31 (0.28)0.34 (0.25)0.13 (0.26)0.27 (0.3)0.2 (0.22)
S-HDL-P0.36 (0.24)0.27 (0.22)−0.01 (0.22)0.1 (0.31)0.48 (0.17)
S-HDL-TG−0.13 (0.25)0.77 (0.13)−0.66 (0.15)0.13 (0.28)1.03 (0.07)
M-HDL-C0.65 (0.14)−0.18 (0.2)0.81 (0.09)−0.09 (0.25)−0.34 (0.17)
M-HDL-CE0.68 (0.14)−0.23 (0.21)0.57 (0.12)−0.24 (0.24)−0.32 (0.18)
M-HDL-FC0.67 (0.12)−0.08 (0.21)0.83 (0.08)0.04 (0.24)−0.28 (0.18)
M-HDL-L0.71 (0.15)0.02 (0.27)0.52 (0.17)−0.03 (0.29)−0.19 (0.25)
M-HDL-P0.75 (0.12)0.15 (0.23)0.46 (0.14)0.08 (0.26)0 (0.19)
M-HDL-PL0.69 (0.13)0.04 (0.22)0.65 (0.11)0.02 (0.25)−0.04 (0.19)
L-HDL-C0.76 (0.11)−0.42 (0.13)0.95 (0.02)−0.1 (0.18)−0.62 (0.09)
L-HDL-CE0.82 (0.1)−0.4 (0.12)0.93 (0.04)−0.16 (0.17)−0.62 (0.09)
L-HDL-FC0.66 (0.12)−0.46 (0.13)0.92 (0.03)−0.13 (0.18)−0.7 (0.08)
L-HDL-L0.81 (0.11)−0.29 (0.15)0.74 (0.07)−0.15 (0.18)−0.56 (0.12)
L-HDL-P0.79 (0.09)−0.35 (0.13)0.82 (0.05)−0.12 (0.16)−0.61 (0.09)
L-HDL-PL0.77 (0.09)−0.34 (0.13)0.79 (0.05)−0.12 (0.17)−0.61 (0.09)
XL-HDL-C0.75 (0.16)−0.25 (0.19)0.9 (0.1)0.4 (0.27)−0.63 (0.13)
XL-HDL-CE0.82 (0.16)−0.17 (0.19)0.82 (0.09)0.41 (0.27)−0.54 (0.12)
XL-HDL-FC0.72 (0.14)−0.37 (0.18)0.94 (0.08)0.17 (0.23)−0.71 (0.11)
XL-HDL-L0.93 (0.16)−0.08 (0.25)0.68 (0.14)0.1 (0.27)−0.35 (0.2)
XL-HDL-P0.81 (0.13)−0.32 (0.16)0.86 (0.08)0.17 (0.21)−0.69 (0.11)
XL-HDL-PL0.76 (0.12)−0.41 (0.15)0.83 (0.07)−0.09 (0.18)−0.7 (0.09)
XL-HDL-TG0.72 (0.13)0.49 (0.17)0.33 (0.13)0.13 (0.26)0.3 (0.15)
HDL-D0.7 (0.11)−0.36 (0.13)0.8 (0.06)−0.08 (0.17)−0.64 (0.09)
IDL-C0.38 (0.21)0.58 (0.19)0.07 (0.19)0.8 (0.14)0.39 (0.17)
IDL-FC0.23 (0.2)0.78 (0.12)−0.05 (0.17)0.61 (0.19)0.44 (0.15)
IDL-L0.38 (0.23)0.65 (0.18)0.05 (0.2)0.64 (0.2)0.47 (0.17)
IDL-P0.31 (0.2)0.66 (0.14)−0.04 (0.17)0.82 (0.13)0.49 (0.14)
IDL-PL0.25 (0.23)0.83 (0.1)−0.12 (0.19)0.7 (0.19)0.64 (0.15)
IDL-TG0.22 (0.18)0.82 (0.08)−0.2 (0.13)0.56 (0.15)0.67 (0.08)
S-LDL-C0.11 (0.28)0.66 (0.18)−0.16 (0.22)0.44 (0.34)0.58 (0.14)
S-LDL-L0.26 (0.23)0.66 (0.17)−0.06 (0.21)0.62 (0.21)0.58 (0.13)
S-LDL-P0.34 (0.2)0.68 (0.15)−0.02 (0.19)0.63 (0.18)0.58 (0.13)
M-LDL-C0.15 (0.26)0.63 (0.18)0.22 (0.22)0.87 (0.08)0.13 (0.23)
M-LDL-CE0.3 (0.23)0.61 (0.2)0.05 (0.21)0.65 (0.2)0.45 (0.16)
M-LDL-L0.29 (0.22)0.63 (0.18)0.01 (0.21)0.66 (0.19)0.5 (0.15)
M-LDL-P0.29 (0.23)0.63 (0.18)−0.01 (0.21)0.65 (0.21)0.51 (0.15)
M-LDL-PL0.2 (0.24)0.69 (0.16)0.11 (0.2)0.89 (0.06)0.18 (0.22)
L-LDL-C0.25 (0.24)0.58 (0.21)0.25 (0.22)0.68 (0.19)0.23 (0.21)
L-LDL-CE0.3 (0.23)0.58 (0.22)0.05 (0.21)0.65 (0.21)0.41 (0.17)
L-LDL-FC0.31 (0.24)0.57 (0.22)0.33 (0.23)0.7 (0.18)0.13 (0.23)
L-LDL-L0.31 (0.23)0.61 (0.2)0.04 (0.21)0.65 (0.21)0.44 (0.17)
L-LDL-P0.31 (0.23)0.63 (0.19)0.02 (0.21)0.65 (0.21)0.47 (0.16)
L-LDL-PL0.27 (0.25)0.61 (0.2)0.24 (0.22)0.67 (0.2)0.27 (0.2)
LDL-D−0.33 (0.25)−0.22 (0.23)−0.15 (0.21)−0.15 (0.29)−0.37 (0.16)
XS-VLDL-L0.25 (0.23)0.8 (0.08)−0.2 (0.17)0.61 (0.14)0.73 (0.09)
XS-VLDL-P0.17 (0.18)0.83 (0.07)−0.26 (0.13)0.57 (0.13)0.71 (0.07)
XS-VLDL-PL0.21 (0.19)0.78 (0.09)−0.15 (0.15)0.74 (0.14)0.57 (0.11)
XS-VLDL-TG0.06 (0.18)0.83 (0.08)−0.37 (0.11)0.56 (0.13)0.85 (0.04)
S-VLDL-FC−0.08 (0.2)0.94 (0.05)−0.49 (0.12)0.59 (0.12)0.92 (0.03)
S-VLDL-L−0.12 (0.24)0.7 (0.08)−0.46 (0.15)0.5 (0.14)0.8 (0.05)
S-VLDL-P−0.09 (0.19)0.78 (0.07)−0.48 (0.11)0.5 (0.14)0.95 (0.02)
S-VLDL-PL−0.03 (0.2)0.82 (0.08)−0.43 (0.12)0.44 (0.17)0.92 (0.03)
S-VLDL-TG−0.1 (0.2)0.9 (0.08)−0.49 (0.11)0.49 (0.15)0.98 (0.01)
S-VLDL-C0.01 (0.2)0.9 (0.06)−0.39 (0.13)0.61 (0.15)0.89 (0.05)
M-VLDL-C−0.01 (0.2)0.8 (0.09)−0.47 (0.12)0.41 (0.18)0.95 (0.02)
M-VLDL-CE0.01 (0.19)0.78 (0.08)−0.43 (0.12)0.5 (0.15)0.9 (0.03)
M-VLDL-FC0 (0.21)0.83 (0.09)−0.48 (0.12)0.4 (0.18)0.97 (0.01)
M-VLDL-L−0.1 (0.24)0.66 (0.11)−0.48 (0.15)0.4 (0.18)0.8 (0.05)
M-VLDL-P−0.06 (0.19)0.78 (0.1)−0.46 (0.12)0.43 (0.16)0.98 (0.02)
M-VLDL-PL0.03 (0.21)0.85 (0.09)−0.48 (0.12)0.4 (0.18)0.98 (0.01)
M-VLDL-TG−0.02 (0.21)0.82 (0.11)−0.5 (0.13)0.33 (0.19)0.98 (0.02)
L-VLDL-C−0.05 (0.2)0.83 (0.12)−0.55 (0.12)0.36 (0.19)1 (0.02)
L-VLDL-CE0 (0.19)0.78 (0.12)−0.44 (0.12)0.43 (0.19)0.93 (0.03)
L-VLDL-FC−0.03 (0.2)0.84 (0.12)−0.53 (0.13)0.36 (0.19)1 (0.02)
L-VLDL-L−0.06 (0.24)0.66 (0.14)−0.47 (0.16)0.36 (0.2)0.86 (0.05)
L-VLDL-P−0.02 (0.21)0.72 (0.12)−0.44 (0.13)0.33 (0.18)0.98 (0.02)
L-VLDL-PL0.01 (0.21)0.86 (0.12)−0.53 (0.13)0.3 (0.2)1.04 (0.03)
L-VLDL-TG−0.06 (0.21)0.78 (0.12)−0.54 (0.13)0.26 (0.19)1 (0.02)
XL-VLDL-L−0.08 (0.24)0.7 (0.15)−0.52 (0.16)0.43 (0.2)0.85 (0.05)
XL-VLDL-P−0.06 (0.2)0.76 (0.12)−0.48 (0.13)0.44 (0.18)0.95 (0.03)
XL-VLDL-PL−0.09 (0.23)0.82 (0.13)−0.62 (0.15)0.32 (0.21)1.06 (0.04)
XL-VLDL-TG−0.14 (0.21)0.86 (0.13)−0.65 (0.13)0.34 (0.19)1.03 (0.04)
XXL-VLDL-L−0.07 (0.25)0.65 (0.16)−0.5 (0.17)0.38 (0.22)0.83 (0.06)
XXL-VLDL-P0.17 (0.2)0.72 (0.15)−0.3 (0.15)0.39 (0.21)0.86 (0.07)
XXL-VLDL-PL−0.3 (0.24)0.66 (0.17)−0.8 (0.16)0.22 (0.21)1.06 (0.06)
XXL-VLDL-TG−0.21 (0.25)0.64 (0.16)−0.7 (0.15)0.22 (0.22)1.08 (0.05)
VLDL-D−0.22 (0.2)0.55 (0.14)−0.53 (0.12)0.12 (0.19)0.86 (0.04)
Appendix 3—table 1
Three-sample Mendelian randomization designs.
MR designSelectionExposureOutcomeReported in
Univariable(traditional selection)GERADavisCARDIoGRAMplusC4DAppendix 3—table 24
GERADavisUK BiobankAppendix 3—table 24
GERAKettunenUK BiobankAppendix 3—table 24
GLGCDavisUK BiobankAppendix 3—table 24
Univariable(subfraction selection)DavisKettunenUK BiobankFigure 2; Appendix 3—figure 1 and Appendix 3—table 24
KettunenDavisUK BiobankAppendix 3—figure 1 and Appendix 3—table 24
MultivariableDavis, GERAKettunen, GLGCCARDIoGRAMplusC4D+ UK BiobankFigure 2, Table 2; Appendix 3—figure 1 and Appendix 3—table 24
Appendix 3—table 2
Mendelian randomization results using all selected SNPs (univariable MR using RAPS and multivariable MR using GRAPPLE).
Method: RAPS/GRAPPLE + All SNPs
ScreeningGERAGERAGERAGLGCDavisKettunenGERA + DavisGERA + Davis
ExposureDavisDavisKettunenDavisKettunenDavisGLGC + KettunenGLGC + Kettunen
OutcomeCADUKBUKBUKBUKBUKBCAD + UKBCAD + UKB
AdjustedHDL-C + LDL-C + TGApoA1 + ApoB + TG
VLDL traits
TG0.258 (0.053)0.296 (0.075)NA0.262 (0.06)NA0.289 (0.068)NANA
VLDL-D-0.099 (0.049)0.028 (0.074)0.072 (0.073)0.116 (0.065)-0.163 (0.067)-0.204 (0.071)-0.588 (0.094)-0.32 (0.112)
XS-VLDL-LNANA0.368 (0.064)NA0.429 (0.059)NA0.132 (0.119)0.084 (0.141)
XS-VLDL-P0.17 (0.031)0.26 (0.048)0.367 (0.065)0.248 (0.047)0.429 (0.06)0.338 (0.056)0.118 (0.125)0.061 (0.158)
XS-VLDL-PL0.191 (0.034)0.284 (0.055)0.386 (0.069)0.278 (0.052)0.449 (0.049)0.435 (0.049)0.159 (0.12)0.253 (0.135)
XS-VLDL-TG0.201 (0.034)0.3 (0.053)0.388 (0.068)0.283 (0.046)0.372 (0.063)0.326 (0.055)-0.157 (0.187)-0.248 (0.15)
S-VLDL-C0.294 (0.06)0.343 (0.076)NA0.322 (0.063)NA0.424 (0.094)-1.035 (0.323)-1.265 (0.568)
S-VLDL-FC0.243 (0.051)0.303 (0.068)0.389 (0.079)0.286 (0.056)0.489 (0.071)0.416 (0.074)-1.027 (0.337)-0.489 (0.213)
S-VLDL-LNANA0.356 (0.075)NA0.376 (0.072)NA-0.898 (0.28)-1.629 (0.586)
S-VLDL-P0.226 (0.047)0.288 (0.068)0.343 (0.074)0.261 (0.054)0.359 (0.069)0.271 (0.094)-1.245 (0.463)-1.644 (0.606)
S-VLDL-PL0.228 (0.047)0.294 (0.067)0.372 (0.074)0.273 (0.054)0.365 (0.066)0.336 (0.063)-0.613 (0.182)-1.213 (0.478)
S-VLDL-TG0.223 (0.049)0.283 (0.071)0.323 (0.073)0.25 (0.055)0.327 (0.071)0.275 (0.067)NaN-0.301 (0.108)
M-VLDL-C0.253 (0.053)0.304 (0.078)0.327 (0.074)0.276 (0.06)0.368 (0.07)0.312 (0.079)-1.433 (0.451)-0.373 (0.118)
M-VLDL-CE0.248 (0.051)0.309 (0.074)0.344 (0.077)0.285 (0.058)0.369 (0.073)0.295 (0.069)-1.035 (0.293)-0.995 (0.338)
M-VLDL-FC0.245 (0.058)0.283 (0.082)0.31 (0.076)0.259 (0.063)0.341 (0.069)0.341 (0.068)-1.412 (0.444)-0.799 (0.311)
M-VLDL-LNANA0.311 (0.079)NA0.358 (0.078)NA-1.878 (0.75)-0.298 (0.098)
M-VLDL-P0.25 (0.062)0.282 (0.083)0.305 (0.081)0.247 (0.065)0.293 (0.089)0.269 (0.065)-1.974 (0.745)-0.312 (0.096)
M-VLDL-PL0.248 (0.056)0.295 (0.077)0.318 (0.075)0.259 (0.06)0.351 (0.071)0.31 (0.063)-2.012 (0.943)-0.297 (0.106)
M-VLDL-TG0.205 (0.064)0.248 (0.087)0.3 (0.082)0.224 (0.067)0.275 (0.092)0.246 (0.074)-2.133 (0.879)-0.806 (0.455)
L-VLDL-C0.299 (0.067)0.304 (0.1)0.297 (0.081)0.291 (0.077)0.289 (0.085)0.317 (0.077)-1.254 (0.297)-0.609 (0.337)
L-VLDL-CE0.247 (0.061)0.282 (0.088)0.282 (0.082)0.282 (0.072)0.285 (0.082)0.3 (0.112)-1.081 (0.282)-0.673 (0.217)
L-VLDL-FC0.316 (0.076)0.294 (0.108)0.311 (0.083)0.287 (0.081)0.351 (0.087)0.298 (0.078)-1.274 (0.308)-0.619 (0.291)
L-VLDL-LNANA0.36 (0.096)NA0.32 (0.102)NA-1.277 (0.313)-0.532 (0.278)
L-VLDL-P0.268 (0.073)0.287 (0.103)0.281 (0.085)0.262 (0.075)0.219 (0.086)0.255 (0.082)-1.357 (0.344)-0.617 (0.229)
L-VLDL-PL0.322 (0.071)0.318 (0.102)0.346 (0.089)0.283 (0.077)0.397 (0.101)0.351 (0.076)NaN-0.287 (0.104)
L-VLDL-TG0.243 (0.077)0.238 (0.104)0.332 (0.094)0.246 (0.08)0.26 (0.103)0.324 (0.082)-1.428 (0.372)-0.252 (0.091)
XL-VLDL-LNANA0.289 (0.098)NA0.435 (0.14)NA-1.069 (0.203)-0.577 (0.249)
XL-VLDL-P0.27 (0.074)0.262 (0.099)0.281 (0.093)0.279 (0.084)0.404 (0.122)0.251 (0.084)-1.209 (0.238)-0.373 (0.109)
XL-VLDL-PL0.446 (0.09)0.344 (0.13)0.31 (0.093)0.361 (0.118)0.375 (0.12)0.408 (0.102)-1.214 (0.257)-0.583 (0.268)
XL-VLDL-TG0.294 (0.092)0.229 (0.109)0.261 (0.094)0.284 (0.095)0.365 (0.111)0.319 (0.093)-1.071 (0.205)-0.603 (0.248)
XXL-VLDL-LNANA0.397 (0.108)NA0.312 (0.108)NA-1.355 (0.318)-0.402 (0.144)
XXL-VLDL-P0.308 (0.08)0.327 (0.096)0.378 (0.097)0.297 (0.088)0.32 (0.101)0.227 (0.073)-1.639 (0.502)-1.089 (0.449)
XXL-VLDL-PL0.338 (0.091)0.346 (0.103)0.342 (0.103)0.351 (0.103)0.282 (0.114)0.317 (0.086)-1.259 (0.262)-0.814 (0.344)
XXL-VLDL-TG0.384 (0.108)0.374 (0.124)0.348 (0.1)0.433 (0.121)0.304 (0.138)0.359 (0.18)-1.202 (0.262)-1.075 (0.402)
IDL/LDL traits
LDL-C0.523 (0.043)0.512 (0.053)0.514 (0.042)0.473 (0.055)0.435 (0.048)0.464 (0.048)NA0.319 (0.182)
ApoB0.605 (0.056)0.55 (0.062)0.551 (0.052)0.543 (0.069)0.61 (0.066)0.613 (0.06)-0.532 (0.191)NA
LDL-D0.271 (0.215)0.452 (0.299)2.064 (0.233)0.831 (0.684)0.328 (0.073)0.201 (0.055)0.145 (0.061)0.119 (0.071)
S-LDL-C0.624 (0.053)0.589 (0.061)0.539 (0.048)0.537 (0.067)0.474 (0.056)0.48 (0.05)-0.282 (0.152)0.08 (0.238)
S-LDL-LNANA0.561 (0.047)NA0.473 (0.057)NA-0.251 (0.145)-0.005 (0.29)
S-LDL-P0.621 (0.057)0.581 (0.065)0.56 (0.049)0.558 (0.073)0.459 (0.061)0.546 (0.063)-0.266 (0.151)-0.362 (0.596)
M-LDL-C0.648 (0.055)0.607 (0.062)0.545 (0.044)0.545 (0.068)0.455 (0.049)0.557 (0.054)-0.271 (0.162)-0.169 (0.909)
M-LDL-CE0.643 (0.056)0.601 (0.062)0.564 (0.042)0.545 (0.069)0.467 (0.05)0.55 (0.055)-0.088 (0.188)NaN
M-LDL-LNANA0.559 (0.042)NA0.461 (0.049)NA-0.069 (0.191)NaN
M-LDL-P0.638 (0.056)0.597 (0.062)0.557 (0.043)0.54 (0.069)0.472 (0.051)0.46 (0.05)-0.179 (0.174)0.432 (0.31)
M-LDL-PL0.658 (0.063)0.605 (0.067)0.556 (0.047)0.571 (0.077)0.506 (0.053)0.559 (0.057)-0.407 (0.162)-0.566 (0.839)
L-LDL-C0.627 (0.053)0.577 (0.059)0.515 (0.042)0.504 (0.063)0.465 (0.048)0.488 (0.052)-0.059 (0.261)NaN
L-LDL-CE0.638 (0.055)0.589 (0.06)0.555 (0.041)0.514 (0.065)0.463 (0.049)0.493 (0.054)0.116 (0.321)0.461 (0.213)
L-LDL-FC0.609 (0.051)0.557 (0.057)0.503 (0.041)0.491 (0.06)0.468 (0.047)0.457 (0.052)0.223 (0.315)NaN
L-LDL-LNANA0.543 (0.04)NA0.468 (0.047)NA0.167 (0.273)NaN
L-LDL-P0.606 (0.052)0.559 (0.058)0.545 (0.041)0.49 (0.062)0.484 (0.046)0.494 (0.048)0.084 (0.213)NaN
L-LDL-PL0.61 (0.053)0.558 (0.058)0.515 (0.043)0.492 (0.063)0.528 (0.048)0.502 (0.052)-0.036 (0.195)NaN
IDL-C0.596 (0.054)0.55 (0.059)0.562 (0.042)0.481 (0.064)0.511 (0.047)0.423 (0.051)0.192 (0.229)0.769 (0.501)
IDL-FC0.586 (0.054)0.539 (0.059)0.525 (0.044)0.494 (0.063)0.44 (0.044)0.402 (0.05)0.19 (0.156)0.33 (0.127)
IDL-LNANA0.57 (0.043)NA0.494 (0.048)NA0.148 (0.175)0.444 (0.328)
IDL-P0.566 (0.052)0.536 (0.059)0.575 (0.044)0.488 (0.065)0.434 (0.049)0.412 (0.051)0.153 (0.148)0.292 (0.173)
IDL-PL0.583 (0.052)0.533 (0.058)0.532 (0.045)0.489 (0.064)0.471 (0.047)0.396 (0.05)0.153 (0.18)0.406 (0.184)
IDL-TG0.603 (0.066)0.595 (0.075)0.658 (0.063)0.567 (0.085)0.432 (0.056)0.315 (0.053)0.11 (0.103)0.047 (0.135)
HDL traits
HDL-C-0.117 (0.031)-0.199 (0.045)-0.136 (0.055)-0.317 (0.052)-0.045 (0.059)-0.108 (0.05)NANaN
ApoA1-0.119 (0.042)-0.193 (0.06)0.023 (0.058)-0.264 (0.071)0.075 (0.064)-0.13 (0.068)-0.481 (0.271)NA
HDL-D-0.008 (0.027)-0.124 (0.041)0.004 (0.046)-0.092 (0.048)0.067 (0.045)0.007 (0.041)0.333 (0.114)0.296 (0.1)
S-HDL-LNANA-0.098 (0.095)NA-0.037 (0.085)NA-0.312 (0.106)-0.224 (0.087)
S-HDL-P-0.265 (0.084)-0.362 (0.113)-0.13 (0.092)-0.317 (0.119)-0.053 (0.081)-0.08 (0.094)-0.331 (0.095)-0.24 (0.083)
S-HDL-TG0.354 (0.072)0.386 (0.088)0.65 (0.089)0.475 (0.097)0.351 (0.087)0.283 (0.073)0.253 (0.637)-0.044 (0.466)
M-HDL-C-0.323 (0.058)-0.43 (0.079)-0.364 (0.085)-0.376 (0.091)-0.46 (0.104)-0.434 (0.075)-0.508 (0.165)-0.442 (0.143)
M-HDL-CE-0.333 (0.058)-0.458 (0.078)-0.372 (0.09)-0.385 (0.087)-0.542 (0.105)-0.443 (0.071)-0.487 (0.157)-0.413 (0.137)
M-HDL-FC-0.275 (0.065)-0.319 (0.08)-0.262 (0.083)-0.313 (0.092)-0.313 (0.094)-0.409 (0.082)-0.649 (0.225)-0.408 (0.166)
M-HDL-LNANA-0.311 (0.095)NA-0.474 (0.123)NA-0.606 (0.188)-0.485 (0.155)
M-HDL-P-0.298 (0.06)-0.394 (0.086)-0.273 (0.101)-0.373 (0.1)-0.565 (0.131)-0.307 (0.079)-0.694 (0.204)-0.472 (0.166)
M-HDL-PL-0.265 (0.058)-0.346 (0.083)-0.25 (0.09)-0.335 (0.096)-0.358 (0.104)-0.3 (0.072)-0.632 (0.191)-0.486 (0.171)
L-HDL-C-0.067 (0.03)-0.144 (0.044)-0.139 (0.051)-0.144 (0.05)-0.147 (0.052)-0.049 (0.045)0.516 (0.213)0.575 (0.204)
L-HDL-CE-0.063 (0.03)-0.144 (0.044)-0.116 (0.051)-0.149 (0.051)-0.134 (0.051)-0.094 (0.047)0.519 (0.23)0.61 (0.206)
L-HDL-FC-0.082 (0.03)-0.144 (0.045)-0.114 (0.053)-0.128 (0.053)-0.13 (0.051)-0.03 (0.047)0.518 (0.181)0.59 (0.148)
L-HDL-LNANA-0.108 (0.05)NA-0.132 (0.052)NA0.457 (0.189)0.541 (0.184)
L-HDL-P-0.071 (0.028)-0.146 (0.042)-0.111 (0.05)-0.13 (0.049)-0.083 (0.05)-0.1 (0.043)0.422 (0.191)0.476 (0.155)
L-HDL-PL-0.087 (0.029)-0.161 (0.043)-0.141 (0.051)-0.142 (0.051)-0.105 (0.053)-0.092 (0.044)0.443 (0.202)0.51 (0.169)
XL-HDL-C0.055 (0.046)-0.013 (0.068)0.11 (0.066)0.064 (0.073)0.048 (0.069)0.112 (0.068)0.474 (0.223)0.565 (0.196)
XL-HDL-CE0.064 (0.044)0.006 (0.066)0.129 (0.066)0.08 (0.07)0.057 (0.068)0.046 (0.075)0.426 (0.177)0.511 (0.206)
XL-HDL-FC0.009 (0.039)-0.05 (0.059)0.066 (0.058)-0.026 (0.067)0.102 (0.06)0.049 (0.066)0.433 (0.16)0.609 (0.159)
XL-HDL-LNANA0.073 (0.055)NA0.038 (0.058)NA0.358 (0.154)0.481 (0.141)
XL-HDL-P0.038 (0.033)-0.022 (0.049)0.112 (0.057)0.017 (0.056)0.083 (0.055)0.023 (0.057)0.41 (0.139)0.39 (0.135)
XL-HDL-PL0.029 (0.031)-0.031 (0.046)0.037 (0.05)0.005 (0.055)0.038 (0.052)0.013 (0.046)0.343 (0.118)0.466 (0.12)
XL-HDL-TG0.092 (0.027)0.112 (0.041)0.14 (0.047)0.135 (0.047)0.191 (0.042)0.136 (0.039)0.147 (0.074)0.165 (0.086)
Appendix 3—table 3
Mendelian randomization results using genome-wide significant SNPs and inverse variance weighted (IVW) estimator.
Method: IVW + Significant SNPs
SelectionGERAGERAGERAGLGCDavisKettunen
ExposureDavisDavisKettunenDavisKettunenDavis
OutcomeCADUKBUKBUKBUKBUKB
VLDL traits
TG0.184 (0.051)0.278 (0.076)NA0.309 (0.074)NA0.207 (0.064)
VLDL-D0.044 (0.06)0.052 (0.09)0.038 (0.102)0.118 (0.091)-0.083 (0.16)-0.083 (0.138)
XS-VLDL-LNANA0.353 (0.08)NA0.372 (0.083)NA
XS-VLDL-P0.162 (0.04)0.256 (0.059)0.352 (0.081)0.273 (0.063)0.374 (0.084)0.373 (0.095)
XS-VLDL-PL0.165 (0.046)0.262 (0.069)0.37 (0.088)0.27 (0.075)0.443 (0.048)0.401 (0.07)
XS-VLDL-TG0.179 (0.041)0.277 (0.061)0.362 (0.082)0.288 (0.062)0.335 (0.076)0.314 (0.08)
S-VLDL-C0.237 (0.053)0.343 (0.08)NA0.339 (0.083)NA0.443 (0.116)
S-VLDL-FC0.21 (0.05)0.307 (0.076)0.344 (0.098)0.314 (0.076)0.262 (0.122)0.397 (0.116)
S-VLDL-LNANA0.318 (0.095)NA0.27 (0.106)NA
S-VLDL-P0.188 (0.049)0.274 (0.074)0.311 (0.093)0.29 (0.072)0.266 (0.103)0.331 (0.142)
S-VLDL-PL0.198 (0.048)0.291 (0.072)0.342 (0.091)0.3 (0.072)0.281 (0.089)0.331 (0.125)
S-VLDL-TG0.174 (0.051)0.255 (0.076)0.296 (0.094)0.28 (0.073)0.261 (0.102)0.262 (0.093)
M-VLDL-C0.188 (0.053)0.265 (0.08)0.305 (0.096)0.287 (0.077)0.361 (0.078)0.32 (0.134)
M-VLDL-CE0.203 (0.051)0.285 (0.077)0.32 (0.098)0.295 (0.076)0.264 (0.094)0.291 (0.125)
M-VLDL-FC0.165 (0.056)0.233 (0.084)0.292 (0.098)0.27 (0.08)0.3 (0.084)0.303 (0.104)
M-VLDL-LNANA0.265 (0.104)NA0.357 (0.096)NA
M-VLDL-P0.153 (0.056)0.214 (0.085)0.276 (0.104)0.258 (0.081)0.322 (0.092)0.268 (0.074)
M-VLDL-PL0.163 (0.054)0.23 (0.082)0.296 (0.097)0.266 (0.078)0.302 (0.084)0.289 (0.095)
M-VLDL-TG0.14 (0.058)0.196 (0.087)0.268 (0.107)0.247 (0.083)0.327 (0.093)0.245 (0.091)
L-VLDL-C0.177 (0.06)0.24 (0.091)0.288 (0.106)0.286 (0.089)0.108 (0.223)0.31 (0.084)
L-VLDL-CE0.178 (0.057)0.245 (0.087)0.262 (0.105)0.279 (0.086)0.182 (0.187)0.299 (0.077)
L-VLDL-FC0.176 (0.063)0.242 (0.094)0.295 (0.108)0.298 (0.091)0.321 (0.101)0.314 (0.082)
L-VLDL-LNANA0.291 (0.119)NA0.125 (0.232)NA
L-VLDL-P0.164 (0.062)0.227 (0.093)0.269 (0.108)0.275 (0.09)0.332 (0.127)0.247 (0.076)
L-VLDL-PL0.173 (0.061)0.23 (0.092)0.308 (0.115)0.284 (0.088)0.32 (0.127)0.302 (0.079)
L-VLDL-TG0.149 (0.063)0.202 (0.095)0.268 (0.118)0.267 (0.092)0.33 (0.131)0.302 (0.08)
XL-VLDL-LNANA0.263 (0.123)NA0.365 (0.286)NA
XL-VLDL-P0.149 (0.063)0.206 (0.095)0.247 (0.122)0.268 (0.096)0.346 (0.28)0.245 (0.077)
XL-VLDL-PL0.176 (0.067)0.243 (0.101)0.292 (0.119)0.323 (0.101)0.333 (0.265)0.344 (0.133)
XL-VLDL-TG0.151 (0.066)0.205 (0.1)0.241 (0.12)0.282 (0.1)0.323 (0.272)0.249 (0.081)
XXL-VLDL-LNANA0.356 (0.127)NA-0.165 (0.425)NA
XXL-VLDL-P0.228 (0.067)0.35 (0.099)0.372 (0.119)0.376 (0.098)-0.12 (0.389)0.006 (0.153)
XXL-VLDL-PL0.211 (0.07)0.31 (0.105)0.275 (0.125)0.399 (0.107)-0.145 (0.395)0.071 (0.191)
XXL-VLDL-TG0.221 (0.067)0.3 (0.102)0.292 (0.126)0.415 (0.104)0.09 (0.36)0.349 (0.303)
IDL/LDL traits
LDL-C0.427 (0.049)0.431 (0.054)0.409 (0.077)0.409 (0.054)0.416 (0.099)0.422 (0.063)
ApoB0.506 (0.058)0.525 (0.065)0.474 (0.093)0.473 (0.064)0.636 (0.092)0.569 (0.071)
LDL-D0.217 (0.151)0.423 (0.161)1.121 (0.178)0.271 (0.143)0.309 (0.126)0.211 (0.081)
S-LDL-C0.481 (0.056)0.467 (0.063)0.445 (0.087)0.438 (0.063)0.44 (0.128)0.436 (0.076)
S-LDL-LNANA0.44 (0.09)NA0.456 (0.132)NA
S-LDL-P0.501 (0.059)0.494 (0.068)0.449 (0.093)0.472 (0.067)0.49 (0.139)0.588 (0.097)
M-LDL-C0.475 (0.057)0.457 (0.064)0.426 (0.08)0.427 (0.064)0.418 (0.111)0.436 (0.087)
M-LDL-CE0.485 (0.058)0.47 (0.065)0.432 (0.078)0.436 (0.064)0.43 (0.107)0.444 (0.085)
M-LDL-LNANA0.43 (0.08)NA0.43 (0.11)NA
M-LDL-P0.479 (0.057)0.465 (0.064)0.437 (0.081)0.44 (0.064)0.413 (0.122)0.439 (0.093)
M-LDL-PL0.5 (0.063)0.49 (0.071)0.437 (0.087)0.464 (0.07)0.443 (0.132)0.497 (0.099)
L-LDL-C0.449 (0.055)0.436 (0.061)0.432 (0.076)0.411 (0.061)0.409 (0.106)0.417 (0.076)
L-LDL-CE0.464 (0.056)0.451 (0.062)0.426 (0.075)0.422 (0.062)0.416 (0.102)0.433 (0.077)
L-LDL-FC0.425 (0.054)0.411 (0.059)0.424 (0.074)0.393 (0.059)0.387 (0.105)0.394 (0.078)
L-LDL-LNANA0.427 (0.074)NA0.407 (0.103)NA
L-LDL-P0.448 (0.054)0.442 (0.06)0.435 (0.075)0.421 (0.059)0.413 (0.104)0.424 (0.075)
L-LDL-PL0.444 (0.056)0.438 (0.061)0.441 (0.078)0.423 (0.061)0.42 (0.109)0.429 (0.076)
IDL-C0.447 (0.055)0.455 (0.059)0.451 (0.075)0.433 (0.06)0.439 (0.085)0.422 (0.07)
IDL-FC0.429 (0.055)0.439 (0.059)0.468 (0.075)0.414 (0.059)0.431 (0.081)0.402 (0.074)
IDL-LNANA0.467 (0.075)NA0.445 (0.085)NA
IDL-P0.443 (0.055)0.467 (0.06)0.48 (0.077)0.45 (0.059)0.446 (0.088)0.426 (0.071)
IDL-PL0.429 (0.055)0.443 (0.059)0.473 (0.078)0.427 (0.059)0.435 (0.092)0.407 (0.069)
IDL-TG0.461 (0.07)0.518 (0.076)0.625 (0.098)0.494 (0.073)0.342 (0.085)0.34 (0.123)
HDL traits
HDL-C-0.085 (0.044)-0.156 (0.057)-0.146 (0.085)-0.195 (0.06)-0.082 (0.159)-0.015 (0.109)
ApoA1-0.072 (0.054)-0.155 (0.071)-0.036 (0.09)-0.194 (0.074)0.001 (0.192)0.066 (0.158)
HDL-D-0.027 (0.042)-0.071 (0.058)-0.052 (0.073)-0.092 (0.063)0.073 (0.098)0.074 (0.074)
S-HDL-LNANA-0.064 (0.148)NA-0.033 (0.092)NA
S-HDL-P-0.117 (0.087)-0.172 (0.116)-0.13 (0.146)-0.298 (0.117)-0.033 (0.09)-0.115 (0.174)
S-HDL-TG0.224 (0.063)0.317 (0.082)0.496 (0.107)0.344 (0.085)0.334 (0.096)0.286 (0.17)
M-HDL-C-0.214 (0.062)-0.327 (0.078)-0.48 (0.111)-0.39 (0.079)-0.423 (0.175)-0.39 (0.159)
M-HDL-CE-0.227 (0.062)-0.338 (0.077)-0.497 (0.111)-0.4 (0.078)-0.435 (0.194)-0.341 (0.238)
M-HDL-FC-0.158 (0.065)-0.272 (0.084)-0.341 (0.117)-0.337 (0.085)-0.288 (0.218)-0.278 (0.144)
M-HDL-LNANA-0.436 (0.125)NA-0.514 (0.223)NA
M-HDL-P-0.172 (0.066)-0.292 (0.087)-0.414 (0.132)-0.361 (0.089)-0.386 (0.307)-0.18 (0.118)
M-HDL-PL-0.161 (0.064)-0.275 (0.085)-0.38 (0.126)-0.345 (0.087)-0.419 (0.301)-0.2 (0.099)
L-HDL-C-0.047 (0.044)-0.097 (0.059)-0.124 (0.08)-0.133 (0.063)0.022 (0.106)0.021 (0.105)
L-HDL-CE-0.049 (0.044)-0.098 (0.059)-0.12 (0.079)-0.137 (0.063)0.023 (0.112)0.004 (0.106)
L-HDL-FC-0.044 (0.046)-0.094 (0.062)-0.106 (0.082)-0.127 (0.067)0.038 (0.103)0.017 (0.109)
L-HDL-LNANA-0.106 (0.077)NA0.034 (0.102)NA
L-HDL-P-0.045 (0.043)-0.097 (0.058)-0.102 (0.077)-0.125 (0.063)0.009 (0.111)0.025 (0.11)
L-HDL-PL-0.054 (0.044)-0.11 (0.06)-0.115 (0.079)-0.14 (0.064)0.006 (0.115)0.016 (0.115)
XL-HDL-C0.03 (0.06)-0.012 (0.084)0.014 (0.099)-0.05 (0.088)-0.015 (0.165)0.161 (0.101)
XL-HDL-CE0.03 (0.059)-0.009 (0.081)0.025 (0.098)-0.042 (0.086)-0.001 (0.166)0.221 (0.107)
XL-HDL-FC-0.003 (0.056)-0.05 (0.076)-0.001 (0.089)-0.077 (0.081)0.072 (0.11)0.057 (0.092)
XL-HDL-LNANA0.001 (0.085)NA-0.009 (0.138)NA
XL-HDL-P0.015 (0.049)-0.021 (0.067)0.013 (0.088)-0.042 (0.071)0.103 (0.1)0.135 (0.093)
XL-HDL-PL0 (0.047)-0.037 (0.065)-0.026 (0.079)-0.055 (0.069)0.081 (0.088)0.071 (0.069)
XL-HDL-TG0.086 (0.041)0.103 (0.059)0.14 (0.075)0.13 (0.063)0.165 (0.043)0.126 (0.051)
Appendix 3—table 4
Mendelian randomization results using genome-wide significant SNPs and the weighted median estimator.
Method: Weighted median + Significant SNPs
SelectionGERAGERAGERAGLGCDavisKettunen
ExposureDavisDavisKettunenDavisKettunenDavis
OutcomeCADUKBUKBUKBUKBUKB
VLDL traits
TG0.042 (0.055)0.191 (0.072)NA0.228 (0.069)NA0.195 (0.077)
VLDL-D-0.098 (0.052)0.039 (0.095)0.057 (0.11)0.058 (0.093)-0.107 (0.099)-0.052 (0.115)
XS-VLDL-LNANA0.312 (0.076)NA0.393 (0.078)NA
XS-VLDL-P0.101 (0.037)0.23 (0.052)0.303 (0.079)0.229 (0.052)0.409 (0.08)0.253 (0.059)
XS-VLDL-PL0.096 (0.039)0.242 (0.059)0.352 (0.087)0.228 (0.06)0.422 (0.065)0.319 (0.062)
XS-VLDL-TG0.125 (0.041)0.266 (0.057)0.287 (0.079)0.221 (0.056)0.361 (0.084)0.306 (0.069)
S-VLDL-C0.187 (0.059)0.232 (0.075)NA0.256 (0.074)NA0.303 (0.094)
S-VLDL-FC0.152 (0.057)0.207 (0.069)0.289 (0.093)0.227 (0.069)0.316 (0.109)0.279 (0.077)
S-VLDL-LNANA0.282 (0.083)NA0.306 (0.099)NA
S-VLDL-P0.131 (0.057)0.202 (0.069)0.275 (0.085)0.221 (0.062)0.291 (0.093)0.226 (0.078)
S-VLDL-PL0.137 (0.053)0.205 (0.067)0.283 (0.083)0.218 (0.062)0.305 (0.092)0.263 (0.075)
S-VLDL-TG0.112 (0.057)0.204 (0.067)0.216 (0.088)0.229 (0.064)0.267 (0.099)0.244 (0.073)
M-VLDL-C0.12 (0.058)0.2 (0.07)0.255 (0.088)0.213 (0.066)0.303 (0.099)0.224 (0.081)
M-VLDL-CE0.144 (0.054)0.207 (0.071)0.262 (0.087)0.207 (0.068)0.301 (0.098)0.209 (0.072)
M-VLDL-FC0.081 (0.058)0.188 (0.074)0.221 (0.087)0.218 (0.068)0.272 (0.102)0.231 (0.08)
M-VLDL-LNANA0.227 (0.095)NA0.275 (0.109)NA
M-VLDL-P0.047 (0.06)0.191 (0.072)0.221 (0.096)0.226 (0.069)0.31 (0.104)0.257 (0.079)
M-VLDL-PL0.103 (0.056)0.197 (0.071)0.228 (0.089)0.217 (0.064)0.29 (0.104)0.231 (0.078)
M-VLDL-TG-0.005 (0.06)0.199 (0.075)0.224 (0.089)0.222 (0.068)0.318 (0.113)0.233 (0.085)
L-VLDL-C0.109 (0.068)0.2 (0.078)0.237 (0.093)0.231 (0.075)0.242 (0.122)0.262 (0.088)
L-VLDL-CE0.147 (0.063)0.211 (0.079)0.249 (0.09)0.253 (0.073)0.281 (0.11)0.286 (0.081)
L-VLDL-FC0.045 (0.065)0.199 (0.085)0.225 (0.093)0.224 (0.077)0.252 (0.125)0.228 (0.089)
L-VLDL-LNANA0.243 (0.102)NA0.261 (0.122)NA
L-VLDL-P0.041 (0.064)0.209 (0.082)0.224 (0.092)0.21 (0.079)0.289 (0.122)0.223 (0.086)
L-VLDL-PL0.08 (0.063)0.201 (0.08)0.244 (0.101)0.224 (0.077)0.278 (0.123)0.247 (0.092)
L-VLDL-TG-0.008 (0.061)0.215 (0.084)0.225 (0.103)0.161 (0.077)0.286 (0.13)0.277 (0.093)
XL-VLDL-LNANA0.262 (0.111)NANANA
XL-VLDL-P-0.026 (0.063)0.207 (0.091)0.289 (0.102)0.192 (0.088)NA0.209 (0.101)
XL-VLDL-PL-0.006 (0.067)0.197 (0.094)0.253 (0.094)0.213 (0.088)NA0.24 (0.101)
XL-VLDL-TG-0.026 (0.064)0.214 (0.092)0.229 (0.102)0.191 (0.088)NA0.212 (0.099)
XXL-VLDL-LNANA0.316 (0.114)NA-0.156 (0.22)NA
XXL-VLDL-P0.091 (0.071)0.236 (0.089)0.267 (0.1)0.263 (0.088)-0.104 (0.173)0.185 (0.098)
XXL-VLDL-PL0.153 (0.082)0.283 (0.096)0.267 (0.11)0.332 (0.095)-0.139 (0.178)0.126 (0.124)
XXL-VLDL-TG0.126 (0.078)0.266 (0.096)0.244 (0.108)0.339 (0.097)0.227 (0.171)0.23 (0.123)
IDL/LDL traits
LDL-C0.263 (0.053)0.307 (0.066)0.274 (0.05)0.297 (0.063)0.435 (0.072)0.431 (0.067)
ApoB0.365 (0.073)0.472 (0.078)0.381 (0.063)0.375 (0.081)0.624 (0.08)0.565 (0.094)
LDL-D0.306 (0.09)0.413 (0.157)0.467 (0.163)0.271 (0.142)0.294 (0.075)0.193 (0.06)
S-LDL-C0.271 (0.058)0.342 (0.073)0.343 (0.056)0.273 (0.068)0.498 (0.08)0.274 (0.083)
S-LDL-LNANA0.354 (0.061)NA0.449 (0.081)NA
S-LDL-P0.355 (0.063)0.366 (0.078)0.397 (0.069)0.329 (0.08)0.49 (0.089)0.581 (0.098)
M-LDL-C0.283 (0.055)0.313 (0.073)0.299 (0.05)0.244 (0.07)0.474 (0.074)0.297 (0.074)
M-LDL-CE0.27 (0.055)0.333 (0.077)0.299 (0.051)0.255 (0.071)0.437 (0.081)0.311 (0.077)
M-LDL-LNANA0.303 (0.053)NA0.432 (0.079)NA
M-LDL-P0.251 (0.057)0.32 (0.071)0.309 (0.054)0.278 (0.07)0.409 (0.072)0.325 (0.078)
M-LDL-PL0.343 (0.063)0.337 (0.081)0.316 (0.055)0.318 (0.078)0.457 (0.074)0.353 (0.085)
L-LDL-C0.251 (0.052)0.29 (0.067)0.303 (0.048)0.231 (0.063)0.45 (0.075)0.309 (0.071)
L-LDL-CE0.251 (0.054)0.32 (0.068)0.293 (0.052)0.241 (0.066)0.481 (0.074)0.322 (0.077)
L-LDL-FC0.251 (0.048)0.214 (0.061)0.301 (0.049)0.214 (0.062)0.427 (0.068)0.289 (0.065)
L-LDL-LNANA0.289 (0.051)NA0.412 (0.07)NA
L-LDL-P0.281 (0.053)0.321 (0.067)0.29 (0.053)0.244 (0.066)0.42 (0.072)0.351 (0.072)
L-LDL-PL0.286 (0.05)0.32 (0.067)0.313 (0.052)0.298 (0.065)0.413 (0.074)0.35 (0.076)
IDL-C0.283 (0.056)0.349 (0.068)0.315 (0.053)0.313 (0.07)0.51 (0.072)0.383 (0.068)
IDL-FC0.283 (0.053)0.334 (0.066)0.337 (0.053)0.314 (0.065)0.422 (0.067)0.367 (0.064)
IDL-LNANA0.329 (0.056)NA0.494 (0.069)NA
IDL-P0.331 (0.06)0.44 (0.067)0.343 (0.056)0.371 (0.069)0.463 (0.074)0.328 (0.068)
IDL-PL0.265 (0.055)0.332 (0.066)0.344 (0.056)0.316 (0.066)0.451 (0.072)0.359 (0.066)
IDL-TG0.233 (0.067)0.371 (0.086)0.605 (0.078)0.337 (0.085)0.315 (0.082)0.215 (0.057)
HDL traits
HDL-C-0.017 (0.04)-0.167 (0.058)-0.17 (0.072)-0.167 (0.058)-0.096 (0.077)-0.085 (0.07)
ApoA10.094 (0.049)-0.06 (0.076)-0.069 (0.087)-0.167 (0.07)0.005 (0.083)-0.051 (0.121)
HDL-D0.079 (0.034)0.062 (0.061)0.102 (0.064)0.088 (0.061)0.099 (0.061)0.096 (0.058)
S-HDL-LNANA-0.174 (0.113)NANANA
S-HDL-P-0.173 (0.069)0.018 (0.106)-0.171 (0.109)-0.235 (0.113)NA-0.049 (0.108)
S-HDL-TG0.157 (0.061)0.238 (0.085)0.312 (0.105)0.228 (0.086)0.327 (0.105)0.229 (0.076)
M-HDL-C-0.169 (0.054)-0.236 (0.082)-0.264 (0.097)-0.241 (0.077)-0.392 (0.098)-0.266 (0.084)
M-HDL-CE-0.166 (0.053)-0.23 (0.08)-0.271 (0.099)-0.238 (0.075)-0.394 (0.103)-0.23 (0.085)
M-HDL-FC-0.166 (0.055)-0.254 (0.086)-0.281 (0.098)-0.282 (0.087)-0.28 (0.102)-0.22 (0.1)
M-HDL-LNANA-0.296 (0.113)NA-0.448 (0.122)NA
M-HDL-P-0.157 (0.056)-0.199 (0.09)-0.298 (0.112)-0.231 (0.086)-0.291 (0.136)-0.165 (0.131)
M-HDL-PL-0.143 (0.058)-0.183 (0.088)-0.285 (0.108)-0.183 (0.085)-0.321 (0.114)-0.203 (0.12)
L-HDL-C0.086 (0.037)-0.009 (0.066)0.031 (0.083)-0.032 (0.08)0.003 (0.09)0.006 (0.068)
L-HDL-CE0.086 (0.038)-0.011 (0.067)0.075 (0.077)-0.037 (0.076)0.015 (0.091)-0.006 (0.068)
L-HDL-FC0.09 (0.039)-0.005 (0.067)0.079 (0.081)-0.019 (0.076)0.041 (0.078)0.027 (0.074)
L-HDL-LNANA0.074 (0.077)NA0.068 (0.084)NA
L-HDL-P0.081 (0.036)0.046 (0.062)0.075 (0.074)-0.01 (0.066)0.066 (0.07)0.078 (0.064)
L-HDL-PL0.084 (0.039)0 (0.067)0.051 (0.082)-0.021 (0.071)0.054 (0.075)0.074 (0.071)
XL-HDL-C0.163 (0.047)0.122 (0.091)0.136 (0.087)0.132 (0.09)0.02 (0.098)0.161 (0.096)
XL-HDL-CE0.139 (0.044)0.106 (0.088)0.122 (0.09)0.148 (0.085)0.038 (0.091)0.336 (0.092)
XL-HDL-FC0.135 (0.048)0.065 (0.079)0.133 (0.081)0.027 (0.077)0.159 (0.079)0.052 (0.086)
XL-HDL-LNANA0.119 (0.075)NA0.023 (0.078)NA
XL-HDL-P0.115 (0.035)0.087 (0.07)0.12 (0.073)0.129 (0.067)0.16 (0.071)0.15 (0.073)
XL-HDL-PL0.101 (0.037)0.064 (0.07)0.11 (0.072)0.121 (0.069)0.141 (0.069)0.088 (0.065)
XL-HDL-TG0.074 (0.027)0.107 (0.047)0.126 (0.051)0.118 (0.042)0.156 (0.05)0.114 (0.045)
Appendix 3—table 5
Multivariable Mendelian randomization results (adjusted for HDL-C, LDL-C, and TG).
TraitHDL-CLDL-CTGSubfraction
VLDL traits
VLDL-D-0.251 (0.052)0.29 (0.037)0.6 (0.087)-0.588 (0.094)
XS-VLDL-L-0.086 (0.046)0.286 (0.077)0.089 (0.099)0.132 (0.119)
XS-VLDL-P-0.083 (0.045)0.299 (0.078)0.093 (0.106)0.118 (0.125)
XS-VLDL-PL-0.083 (0.046)0.249 (0.098)0.112 (0.076)0.159 (0.12)
XS-VLDL-TG-0.114 (0.046)0.463 (0.079)0.286 (0.173)-0.157 (0.187)
S-VLDL-C-0.267 (0.084)0.754 (0.112)1.033 (0.28)-1.035 (0.323)
S-VLDL-FC-0.195 (0.068)0.898 (0.163)0.935 (0.26)-1.027 (0.337)
S-VLDL-L-0.25 (0.072)0.755 (0.112)0.876 (0.233)-0.898 (0.28)
S-VLDL-P-0.31 (0.101)0.819 (0.157)1.209 (0.4)-1.245 (0.463)
S-VLDL-PL-0.168 (0.051)0.673 (0.074)0.626 (0.159)-0.613 (0.182)
S-VLDL-TG-0.499 (0.305)0.906 (0.34)2.532 (1.57)-2.628 (1.741)
M-VLDL-C-0.201 (0.068)0.808 (0.127)1.472 (0.424)-1.433 (0.451)
M-VLDL-CE-0.168 (0.061)0.799 (0.111)0.996 (0.249)-1.035 (0.293)
M-VLDL-FC-0.2 (0.072)0.658 (0.089)1.469 (0.417)-1.412 (0.444)
M-VLDL-L-0.355 (0.139)0.602 (0.096)1.787 (0.654)-1.878 (0.75)
M-VLDL-P-0.362 (0.124)0.569 (0.08)1.889 (0.676)-1.974 (0.745)
M-VLDL-PL-0.332 (0.141)0.722 (0.159)1.996 (0.869)-2.012 (0.943)
M-VLDL-TG-0.408 (0.153)0.432 (0.061)1.974 (0.772)-2.133 (0.879)
L-VLDL-C-0.216 (0.063)0.509 (0.046)1.163 (0.254)-1.254 (0.297)
L-VLDL-CE-0.272 (0.072)0.465 (0.04)1.038 (0.242)-1.081 (0.282)
L-VLDL-FC-0.144 (0.059)0.493 (0.044)1.233 (0.27)-1.274 (0.308)
L-VLDL-L-0.228 (0.066)0.414 (0.045)1.17 (0.263)-1.277 (0.313)
L-VLDL-P-0.115 (0.056)0.442 (0.046)1.351 (0.317)-1.357 (0.344)
L-VLDL-PL-0.221 (0.111)0.473 (0.07)2.135 (0.948)-2.316 (1.112)
L-VLDL-TG-0.196 (0.066)0.355 (0.05)1.357 (0.322)-1.428 (0.372)
XL-VLDL-L-0.126 (0.049)0.451 (0.04)0.896 (0.159)-1.069 (0.203)
XL-VLDL-P-0.127 (0.053)0.474 (0.043)1.038 (0.183)-1.209 (0.238)
XL-VLDL-PL-0.138 (0.055)0.5 (0.044)1.052 (0.204)-1.214 (0.257)
XL-VLDL-TG-0.129 (0.049)0.424 (0.04)0.944 (0.167)-1.071 (0.205)
XXL-VLDL-L-0.228 (0.067)0.444 (0.043)0.978 (0.207)-1.355 (0.318)
XXL-VLDL-P0.063 (0.076)0.452 (0.05)1.371 (0.384)-1.639 (0.502)
XXL-VLDL-PL-0.185 (0.056)0.371 (0.042)0.997 (0.185)-1.259 (0.262)
XXL-VLDL-TG-0.152 (0.059)0.41 (0.04)0.966 (0.19)-1.202 (0.262)
LDL/IDL traits
ApoB-0.084 (0.046)0.8 (0.146)0.427 (0.101)-0.532 (0.191)
LDL-D-0.057 (0.042)0.367 (0.03)0.21 (0.053)0.145 (0.061)
S-LDL-C-0.062 (0.043)0.614 (0.126)0.261 (0.062)-0.282 (0.152)
S-LDL-L-0.06 (0.044)0.584 (0.118)0.266 (0.068)-0.251 (0.145)
S-LDL-P-0.033 (0.047)0.589 (0.119)0.29 (0.078)-0.266 (0.151)
M-LDL-C-0.082 (0.044)0.623 (0.146)0.203 (0.054)-0.271 (0.162)
M-LDL-CE-0.074 (0.043)0.485 (0.167)0.169 (0.059)-0.088 (0.188)
M-LDL-L-0.071 (0.044)0.444 (0.171)0.19 (0.063)-0.069 (0.191)
M-LDL-P-0.054 (0.044)0.539 (0.153)0.213 (0.063)-0.179 (0.174)
M-LDL-PL-0.081 (0.045)0.747 (0.134)0.232 (0.062)-0.407 (0.162)
L-LDL-C-0.071 (0.049)0.437 (0.242)0.167 (0.054)-0.059 (0.261)
L-LDL-CE-0.07 (0.048)0.277 (0.301)0.149 (0.065)0.116 (0.321)
L-LDL-FC-0.112 (0.057)0.184 (0.304)0.163 (0.053)0.223 (0.315)
L-LDL-L-0.075 (0.049)0.229 (0.26)0.146 (0.068)0.167 (0.273)
L-LDL-P-0.083 (0.046)0.33 (0.2)0.128 (0.064)0.084 (0.213)
L-LDL-PL-0.101 (0.046)0.446 (0.177)0.155 (0.057)-0.036 (0.195)
IDL-C-0.108 (0.057)0.231 (0.215)0.128 (0.064)0.192 (0.229)
IDL-FC-0.107 (0.05)0.23 (0.147)0.123 (0.056)0.19 (0.156)
IDL-L-0.1 (0.05)0.274 (0.161)0.123 (0.069)0.148 (0.175)
IDL-P-0.101 (0.047)0.269 (0.134)0.109 (0.071)0.153 (0.148)
IDL-PL-0.076 (0.048)0.25 (0.162)0.134 (0.071)0.153 (0.18)
IDL-TG-0.083 (0.046)0.314 (0.069)0.103 (0.089)0.11 (0.103)
HDL traits
ApoA10.345 (0.25)0.544 (0.081)0.334 (0.109)-0.481 (0.271)
HDL-D-0.442 (0.124)0.421 (0.033)0.111 (0.055)0.333 (0.114)
S-HDL-L-0.117 (0.046)0.488 (0.044)0.189 (0.054)-0.312 (0.106)
S-HDL-P-0.112 (0.046)0.453 (0.035)0.225 (0.056)-0.331 (0.095)
S-HDL-TG0.002 (0.145)0.314 (0.156)-0.007 (0.469)0.253 (0.637)
M-HDL-C0.179 (0.097)0.36 (0.038)0.147 (0.054)-0.508 (0.165)
M-HDL-CE0.167 (0.087)0.319 (0.036)0.166 (0.055)-0.487 (0.157)
M-HDL-FC0.339 (0.141)0.436 (0.04)0.247 (0.059)-0.649 (0.225)
M-HDL-L0.27 (0.108)0.362 (0.032)0.299 (0.063)-0.606 (0.188)
M-HDL-P0.302 (0.112)0.386 (0.033)0.371 (0.075)-0.694 (0.204)
M-HDL-PL0.311 (0.117)0.402 (0.033)0.333 (0.07)-0.632 (0.191)
L-HDL-C-0.589 (0.211)0.469 (0.039)0.146 (0.055)0.516 (0.213)
L-HDL-CE-0.602 (0.239)0.477 (0.042)0.137 (0.056)0.519 (0.23)
L-HDL-FC-0.573 (0.177)0.437 (0.034)0.171 (0.054)0.518 (0.181)
L-HDL-L-0.556 (0.193)0.437 (0.034)0.142 (0.055)0.457 (0.189)
L-HDL-P-0.515 (0.198)0.417 (0.03)0.133 (0.056)0.422 (0.191)
L-HDL-PL-0.53 (0.201)0.415 (0.034)0.152 (0.055)0.443 (0.202)
XL-HDL-C-0.447 (0.182)0.342 (0.036)0.071 (0.079)0.474 (0.223)
XL-HDL-CE-0.425 (0.146)0.366 (0.038)0.051 (0.069)0.426 (0.177)
XL-HDL-FC-0.459 (0.147)0.377 (0.031)0.097 (0.062)0.433 (0.16)
XL-HDL-L-0.405 (0.146)0.364 (0.031)0.077 (0.068)0.358 (0.154)
XL-HDL-P-0.451 (0.134)0.374 (0.03)0.078 (0.064)0.41 (0.139)
XL-HDL-PL-0.422 (0.119)0.412 (0.033)0.115 (0.055)0.343 (0.118)
XL-HDL-TG-0.186 (0.073)0.336 (0.035)0.045 (0.086)0.147 (0.074)
Appendix 3—table 6
Multivariable Mendelian randomization results (adjusted for ApoA1, ApoB, and TG).
TraitApoA1ApoBTGSubfraction
VLDL traits
VLDL-D-0.227 (0.067)0.545 (0.092)0.208 (0.139)-0.32 (0.112)
XS-VLDL-L-0.123 (0.063)0.53 (0.163)-0.121 (0.085)0.084 (0.141)
XS-VLDL-P-0.121 (0.064)0.553 (0.17)-0.123 (0.088)0.061 (0.158)
XS-VLDL-PL-0.147 (0.066)0.273 (0.138)0.028 (0.05)0.253 (0.135)
XS-VLDL-TG-0.102 (0.06)0.762 (0.168)0.069 (0.055)-0.248 (0.15)
S-VLDL-C-0.384 (0.141)1.426 (0.354)0.606 (0.351)-1.265 (0.568)
S-VLDL-FC-0.188 (0.077)1.001 (0.235)0.081 (0.053)-0.489 (0.213)
S-VLDL-L-0.46 (0.146)1.776 (0.417)0.7 (0.316)-1.629 (0.586)
S-VLDL-P-0.494 (0.159)1.677 (0.386)0.825 (0.372)-1.644 (0.606)
S-VLDL-PL-0.262 (0.097)1.41 (0.343)0.532 (0.261)-1.213 (0.478)
S-VLDL-TG-0.18 (0.069)0.792 (0.121)0.078 (0.051)-0.301 (0.108)
M-VLDL-C-0.157 (0.062)0.867 (0.132)0.085 (0.051)-0.373 (0.118)
M-VLDL-CE-0.221 (0.069)1.224 (0.223)0.47 (0.21)-0.995 (0.338)
M-VLDL-FC-0.222 (0.074)0.902 (0.133)0.482 (0.251)-0.799 (0.311)
M-VLDL-L-0.174 (0.065)0.76 (0.104)0.073 (0.05)-0.298 (0.098)
M-VLDL-P-0.181 (0.065)0.764 (0.1)0.077 (0.051)-0.312 (0.096)
M-VLDL-PL-0.159 (0.065)0.776 (0.116)0.08 (0.051)-0.297 (0.106)
M-VLDL-TG-0.263 (0.106)0.724 (0.094)0.547 (0.406)-0.806 (0.455)
L-VLDL-C-0.218 (0.084)0.732 (0.101)0.352 (0.278)-0.609 (0.337)
L-VLDL-CE-0.293 (0.079)0.781 (0.096)0.405 (0.189)-0.673 (0.217)
L-VLDL-FC-0.197 (0.069)0.737 (0.094)0.365 (0.25)-0.619 (0.291)
L-VLDL-L-0.194 (0.071)0.666 (0.087)0.289 (0.234)-0.532 (0.278)
L-VLDL-P-0.184 (0.061)0.677 (0.086)0.415 (0.217)-0.617 (0.229)
L-VLDL-PL-0.155 (0.063)0.715 (0.095)0.075 (0.051)-0.287 (0.104)
L-VLDL-TG-0.154 (0.062)0.67 (0.083)0.073 (0.05)-0.252 (0.091)
XL-VLDL-L-0.186 (0.066)0.694 (0.088)0.263 (0.19)-0.577 (0.249)
XL-VLDL-P-0.167 (0.061)0.742 (0.088)0.075 (0.05)-0.373 (0.109)
XL-VLDL-PL-0.191 (0.068)0.712 (0.092)0.271 (0.197)-0.583 (0.268)
XL-VLDL-TG-0.195 (0.068)0.666 (0.087)0.334 (0.21)-0.603 (0.248)
XXL-VLDL-L-0.173 (0.066)0.732 (0.098)0.088 (0.052)-0.402 (0.144)
XXL-VLDL-P-0.071 (0.065)0.705 (0.097)0.607 (0.321)-1.089 (0.449)
XXL-VLDL-PL-0.244 (0.082)0.666 (0.091)0.414 (0.257)-0.814 (0.344)
XXL-VLDL-TG-0.3 (0.091)0.694 (0.095)0.627 (0.306)-1.075 (0.402)
IDL/LDL traits
LDL-C-0.119 (0.062)0.247 (0.167)0.066 (0.054)0.319 (0.182)
LDL-D-0.123 (0.06)0.544 (0.091)-0.036 (0.087)0.119 (0.071)
S-LDL-C-0.097 (0.06)0.438 (0.216)0.044 (0.051)0.08 (0.238)
S-LDL-L-0.097 (0.063)0.503 (0.268)0.043 (0.051)-0.005 (0.29)
S-LDL-P-0.059 (0.103)0.932 (0.597)-0.122 (0.112)-0.362 (0.596)
M-LDL-C-0.099 (0.065)0.78 (1.034)-0.172 (0.425)-0.169 (0.909)
M-LDL-CE-0.157 (0.128)-0.346 (2.587)0.195 (0.855)0.854 (2.221)
M-LDL-L-0.123 (0.095)0.247 (1.479)-0.001 (0.445)0.32 (1.293)
M-LDL-P-0.134 (0.07)0.13 (0.286)0.053 (0.052)0.432 (0.31)
M-LDL-PL-0.075 (0.077)1.165 (0.868)-0.248 (0.253)-0.566 (0.839)
L-LDL-C-0.855 (1.68)-5.337 (13.402)2.405 (5.735)5.257 (11.72)
L-LDL-CE-0.151 (0.065)0.129 (0.193)0.061 (0.052)0.461 (0.213)
L-LDL-FC-0.397 (0.219)-1.139 (1.395)0.786 (0.711)1.531 (1.189)
L-LDL-L-0.265 (0.148)-0.854 (1.42)0.41 (0.51)1.266 (1.188)
L-LDL-P-0.258 (0.153)-0.607 (1.225)0.276 (0.402)1.064 (1.029)
L-LDL-PL-0.312 (0.187)-0.741 (1.411)0.39 (0.518)1.227 (1.245)
IDL-C-0.3 (0.123)-0.334 (0.616)0.276 (0.254)0.769 (0.501)
IDL-FC-0.199 (0.069)0.247 (0.118)0.044 (0.049)0.33 (0.127)
IDL-L-0.215 (0.089)0.021 (0.409)0.101 (0.15)0.444 (0.328)
IDL-P-0.175 (0.075)0.214 (0.172)0.04 (0.051)0.292 (0.173)
IDL-PL-0.183 (0.07)0.159 (0.172)0.031 (0.049)0.406 (0.184)
IDL-TG-0.143 (0.075)0.565 (0.146)-0.119 (0.087)0.047 (0.135)
HDL traits
HDL-C-1.513 (1.109)0.982 (0.314)0.27 (0.291)1.446 (1.112)
HDL-D-0.457 (0.138)0.613 (0.073)0.056 (0.049)0.296 (0.1)
S-HDL-L-0.128 (0.059)0.524 (0.062)0.067 (0.05)-0.224 (0.087)
S-HDL-P-0.132 (0.059)0.531 (0.059)0.071 (0.05)-0.24 (0.083)
S-HDL-TG-0.11 (0.113)0.595 (0.221)-0.057 (0.297)-0.044 (0.466)
M-HDL-C0.091 (0.084)0.459 (0.101)-0.1 (0.083)-0.442 (0.143)
M-HDL-CE0.09 (0.078)0.291 (0.083)0.082 (0.05)-0.413 (0.137)
M-HDL-FC0.148 (0.11)0.378 (0.063)0.066 (0.049)-0.408 (0.166)
M-HDL-L0.133 (0.091)0.491 (0.097)-0.029 (0.086)-0.485 (0.155)
M-HDL-P0.129 (0.097)0.501 (0.097)-0.004 (0.09)-0.472 (0.166)
M-HDL-PL0.162 (0.107)0.519 (0.096)-0.037 (0.087)-0.486 (0.171)
L-HDL-C-0.724 (0.232)0.856 (0.132)0.032 (0.093)0.575 (0.204)
L-HDL-CE-0.761 (0.236)0.899 (0.145)0.004 (0.084)0.61 (0.206)
L-HDL-FC-0.749 (0.174)0.842 (0.102)0.094 (0.05)0.59 (0.148)
L-HDL-L-0.717 (0.217)0.815 (0.12)0.023 (0.089)0.541 (0.184)
L-HDL-P-0.653 (0.191)0.749 (0.104)0.057 (0.049)0.476 (0.155)
L-HDL-PL-0.679 (0.201)0.774 (0.109)0.05 (0.049)0.51 (0.169)
XL-HDL-C-0.639 (0.194)0.692 (0.095)-0.058 (0.086)0.565 (0.196)
XL-HDL-CE-0.576 (0.2)0.667 (0.096)-0.077 (0.086)0.511 (0.206)
XL-HDL-FC-0.734 (0.174)0.674 (0.073)0.094 (0.052)0.609 (0.159)
XL-HDL-L-0.652 (0.168)0.733 (0.097)-0.06 (0.084)0.481 (0.141)
XL-HDL-P-0.52 (0.147)0.691 (0.094)-0.075 (0.084)0.39 (0.135)
XL-HDL-PL-0.652 (0.151)0.687 (0.076)0.079 (0.051)0.466 (0.12)
XL-HDL-TG-0.281 (0.111)0.539 (0.09)-0.152 (0.092)0.165 (0.086)
Appendix 3—table 7
Modified Cochran’s Q-statistics (p-values) for the multivariable Mendelian randomization analyses (adjusted for HDL-C, LDL-C, and TG).

DF is short for degrees of freedom.

TraitDFHDL-CLDL-CTGSubfraction
VLDL traits
VLDL-D4327640.8 (0)1918.9 (7.9e-186)877.6 (1.4e-32)840.2 (1.6e-28)
XS-VLDL-L4367983.9 (0)1104.9 (1.1e-59)1935.8 (2.2e-187)926 (1.9e-37)
XS-VLDL-P4367927.8 (0)1066.6 (1.1e-54)1814 (4.8e-167)893.6 (9.6e-34)
XS-VLDL-PL4358291.5 (0)968.1 (1.4e-42)2771.5 (0)849.8 (4.3e-29)
XS-VLDL-TG4317549.8 (0)894.4 (1.3e-34)739.5 (1.3e-18)682.5 (1.2e-13)
S-VLDL-C4298598.1 (0)652.6 (1.7e-11)1220.7 (4.6e-77)541.3 (0.00018)
S-VLDL-FC4347861.2 (0)576 (5.4e-06)519.4 (0.003)507.9 (0.0082)
S-VLDL-L4387105.3 (0)626 (8.5e-09)525.2 (0.0026)514.3 (0.0069)
S-VLDL-P4386686.5 (0)616.5 (3.6e-08)515.6 (0.0061)507.3 (0.012)
S-VLDL-PL4377589.1 (0)702.8 (1e-14)591.5 (1.1e-06)555.1 (0.00011)
S-VLDL-TG4377658.7 (0)612.7 (5.3e-08)498.9 (0.021)494.5 (0.03)
M-VLDL-C4329167.8 (0)740.8 (1.3e-18)558.9 (3.5e-05)551.5 (8.3e-05)
M-VLDL-CE4328055.2 (0)705.9 (1.6e-15)556.6 (4.6e-05)539.7 (0.00031)
M-VLDL-FC4368272.8 (0)814.8 (2.7e-25)528.3 (0.0016)519.1 (0.0037)
M-VLDL-L4297109.2 (0)1269.2 (5.5e-84)532.6 (0.00047)515.9 (0.0025)
M-VLDL-P4368260.7 (0)2059.5 (2.1e-208)527.5 (0.0017)516.8 (0.0046)
M-VLDL-PL4356849.2 (0)599.6 (2.6e-07)496.8 (0.021)493.5 (0.027)
M-VLDL-TG4366123.7 (0)9854.8 (0)532.3 (0.0011)521 (0.0031)
L-VLDL-C4358617.2 (0)8966 (0)654.7 (4.3e-11)561.5 (3.9e-05)
L-VLDL-CE4346636.6 (0)11134 (0)581.6 (2.6e-06)539.5 (0.00041)
L-VLDL-FC4317779.6 (0)6691 (0)595.1 (2.5e-07)562.7 (1.9e-05)
L-VLDL-L4348104.9 (0)5191.4 (0)560.3 (3.9e-05)548.6 (0.00015)
L-VLDL-P4352308 (5.1e-252)10360.3 (0)545.4 (0.00024)537.9 (0.00054)
L-VLDL-PL4308155.4 (0)1310.8 (8.6e-90)491.8 (0.021)489.7 (0.024)
L-VLDL-TG4388581.8 (0)4800.1 (0)569.1 (2.3e-05)559.2 (7.5e-05)
XL-VLDL-L4378686.8 (0)8322.2 (0)674.7 (1.9e-12)620.2 (1.7e-08)
XL-VLDL-P4318550.2 (0)2459.4 (2e-280)608.3 (3.6e-08)588.6 (6.3e-07)
XL-VLDL-PL4317478.2 (0)5042.5 (0)613.3 (1.7e-08)591.6 (4.1e-07)
XL-VLDL-TG4338237.3 (0)9628.9 (0)651.8 (4.6e-11)618.3 (1.1e-08)
XXL-VLDL-L4398476.2 (0)10436.4 (0)652.9 (1.3e-10)570.7 (2.2e-05)
XXL-VLDL-P4371291.3 (2.8e-85)9987.4 (0)540.3 (0.00053)529.5 (0.0016)
XXL-VLDL-PL4369631.8 (0)11287.1 (0)641.6 (4.8e-10)595.5 (5.3e-07)
XXL-VLDL-TG4297809.4 (0)9476.4 (0)595.6 (1.7e-07)564 (1.2e-05)
LDL/IDL traits
ApoB4359220.8 (0)550.1 (0.00014)1809.7 (1.2e-166)535.1 (0.00072)
LDL-D4292909.2 (0)3918.8 (0)2706 (0)1426.1 (2.9e-107)
S-LDL-C4318189.7 (0)569.8 (7.8e-06)4880.9 (0)564.1 (1.6e-05)
S-LDL-L4358403.8 (0)574.4 (7.8e-06)3931.2 (0)564.3 (2.7e-05)
S-LDL-P4317371.4 (0)547.1 (0.00012)3144.7 (0)537.9 (0.00034)
M-LDL-C4309723.7 (0)570.9 (5.8e-06)6568.6 (0)562.9 (1.6e-05)
M-LDL-CE4328442.1 (0)558.3 (3.8e-05)5773.6 (0)549.1 (0.00011)
M-LDL-L4308801.7 (0)555.4 (4e-05)5176.1 (0)548.2 (9.5e-05)
M-LDL-P4298798.9 (0)541.6 (0.00018)5049.7 (0)535.2 (0.00035)
M-LDL-PL4367981.7 (0)573.9 (9.6e-06)4304.8 (0)558.9 (6e-05)
L-LDL-C4328865.2 (0)567.7 (1.2e-05)6179.8 (0)567 (1.3e-05)
L-LDL-CE4338464.3 (0)558.7 (4.1e-05)5731.3 (0)555.6 (5.9e-05)
L-LDL-FC4317481.1 (0)580.6 (1.9e-06)6760.8 (0)580.2 (2e-06)
L-LDL-L4338486.8 (0)604.5 (8.9e-08)5755.8 (0)601.8 (1.3e-07)
L-LDL-P4348310.7 (0)592.1 (6.3e-07)5553.3 (0)584.9 (1.7e-06)
L-LDL-PL4358341.4 (0)588.5 (1.2e-06)5327.8 (0)577.4 (5.3e-06)
IDL-C4347873.9 (0)645.5 (1.7e-10)6336 (0)642.1 (2.9e-10)
IDL-FC4328036 (0)729.5 (1.4e-17)6630.5 (0)725.6 (3e-17)
IDL-L4347869.8 (0)694.5 (2.4e-14)5198.3 (0)689 (7e-14)
IDL-P4369660.5 (0)736.7 (9e-18)5002 (0)726.6 (7.1e-17)
IDL-PL4318432.6 (0)680.6 (1.7e-13)5023 (0)677.4 (3e-13)
IDL-TG4367741.2 (0)1077.5 (4.2e-56)1992.9 (4.9e-197)931.6 (4.4e-38)
HDL traits
ApoA1434494.1 (0.024)511.5 (0.006)932.1 (1.8e-38)492 (0.028)
HDL-D438783.5 (6.6e-22)8500 (0)5713.2 (0)860.1 (9.4e-30)
S-HDL-L4383067.3 (0)4414.6 (0)3763.2 (0)882.2 (3.7e-32)
S-HDL-P4382592.4 (1.1e-301)7652.1 (0)3097.3 (0)951.1 (4.9e-40)
S-HDL-TG425896.9 (6.9e-36)641.3 (5.2e-11)540.1 (0.00013)523 (8e-04)
M-HDL-C437957.6 (5.5e-41)10172.4 (0)4875.5 (0)628.3 (4.9e-09)
M-HDL-CE434955.3 (3.2e-41)1383.1 (1.7e-99)4355.4 (0)648.3 (1e-10)
M-HDL-FC432759.4 (2.4e-20)2989.1 (0)3512.2 (0)538.2 (0.00037)
M-HDL-L435914.2 (3e-36)11535.3 (0)2327.7 (1.7e-255)570.3 (1.3e-05)
M-HDL-P434997.6 (2.3e-46)10709.6 (0)1942.9 (3.2e-189)561.3 (3.4e-05)
M-HDL-PL434977.8 (6.3e-44)9439.9 (0)2566 (1.8e-298)581.3 (2.7e-06)
L-HDL-C434580 (3.2e-06)1257.1 (4.4e-81)4502.7 (0)604.3 (1.1e-07)
L-HDL-CE434549 (0.00014)930.2 (3e-38)5517.2 (0)557.2 (5.6e-05)
L-HDL-FC441627.6 (1.2e-08)8415.3 (0)3594 (0)658.4 (7.9e-11)
L-HDL-L434603.6 (1.2e-07)6743.8 (0)5314.7 (0)623.7 (5.7e-09)
L-HDL-P432601.1 (1.2e-07)7769.3 (0)6024.6 (0)633.2 (8.6e-10)
L-HDL-PL434584.5 (1.8e-06)9935.5 (0)3544.3 (0)611.3 (3.8e-08)
XL-HDL-C430732.9 (3.9e-18)10426.6 (0)2077.7 (1.4e-213)686.9 (4e-14)
XL-HDL-CE430771.4 (9.3e-22)8564.4 (0)2457 (2.2e-280)711.4 (3.3e-16)
XL-HDL-FC432761.8 (1.4e-20)11265.2 (0)2549.4 (3.1e-296)770.9 (1.9e-21)
XL-HDL-L429767.6 (1.6e-21)11490.7 (0)2355.7 (1.2e-262)784.6 (3.4e-23)
XL-HDL-P433724.9 (4.6e-17)11372.5 (0)2539.9 (3.9e-294)798.5 (4.8e-24)
XL-HDL-PL443809.7 (7.8e-24)10093.1 (0)5762 (0)895.4 (7.5e-33)
XL-HDL-TG4321849.1 (3.9e-174)2635.9 (6.5e-312)2240.8 (2.9e-241)1267.8 (4.4e-83)
Appendix 3—table 8
Modified Cochran’s Q-statistics (p-values) for the multivariable Mendelian randomization analyses (adjusted for ApoA1, ApoB, and TG).

DF is short for degrees of freedom.

TraitDFApoA1ApoBTGSubfraction
VLDL traits
VLDL-D2971194.1 (9.1e-108)550 (2.4e-17)573.7 (8.2e-20)606.7 (2.1e-23)
XS-VLDL-L2951185.1 (6.7e-107)927 (2e-66)1151.3 (2.2e-101)887.9 (1.1e-60)
XS-VLDL-P2951194.9 (1.7e-108)900 (1.9e-62)895.5 (8.7e-62)826.7 (6.4e-52)
XS-VLDL-PL2961148.5 (1.2e-100)973.9 (3.2e-73)2104.2 (1.4e-269)961.4 (2.5e-71)
XS-VLDL-TG3021263.7 (1.1e-117)757.9 (4.7e-41)1308.1 (4.4e-125)976.5 (4.6e-72)
S-VLDL-C290988.8 (4.4e-77)394 (4.5e-05)459.8 (7.8e-10)402.6 (1.3e-05)
S-VLDL-FC2961092 (1.4e-91)904 (8.6e-63)1238.7 (2.1e-115)1010.4 (8.1e-79)
S-VLDL-L3011107.9 (1.1e-92)412.3 (2.1e-05)420.8 (5.9e-06)384.7 (0.00078)
S-VLDL-P3011116.6 (4.6e-94)424.8 (3.3e-06)401.3 (9.4e-05)380.6 (0.0013)
S-VLDL-PL2991096 (2.3e-91)428.9 (1.2e-06)446 (7.1e-08)432.1 (7.1e-07)
S-VLDL-TG3001152.4 (4.3e-100)908.5 (1.8e-62)1453.4 (1.8e-150)1303.1 (7.1e-125)
M-VLDL-C2981171.2 (1e-103)824 (7.3e-51)1480 (8.9e-156)1212.5 (1.8e-110)
M-VLDL-CE2981185.4 (4.9e-106)564.4 (1.1e-18)468.9 (9.2e-10)431.6 (6.3e-07)
M-VLDL-FC2981190.4 (7.4e-107)899.8 (1.1e-61)415.2 (8.1e-06)398.8 (8.4e-05)
M-VLDL-L2981144.1 (2.4e-99)869.8 (2.4e-57)1381 (1e-138)1237.4 (1.4e-114)
M-VLDL-P2971121.3 (5.7e-96)821.1 (1.1e-50)1250.5 (4.6e-117)1206.7 (8.1e-110)
M-VLDL-PL2981149.9 (2.8e-100)843.2 (1.5e-53)1391.8 (1.5e-140)1226.3 (9.8e-113)
M-VLDL-TG2961187.4 (5.8e-107)717.3 (5.8e-37)366.3 (0.0033)360.6 (0.006)
L-VLDL-C2951196.5 (9.1e-109)820 (5.6e-51)462.5 (1.5e-09)376.9 (0.00088)
L-VLDL-CE3021183.1 (1.8e-104)844.6 (7.4e-53)541.8 (7.2e-16)441.7 (2.6e-07)
L-VLDL-FC2951172.3 (8.2e-105)851.6 (1.9e-55)460.8 (2.1e-09)406.2 (1.8e-05)
L-VLDL-L2951163.6 (2.2e-103)797 (8.8e-48)406.5 (1.7e-05)391.5 (0.00014)
L-VLDL-P2931160.2 (2e-103)809.5 (5.9e-50)420.2 (1.5e-06)407.9 (1e-05)
L-VLDL-PL2961292 (2.6e-124)833.4 (1.3e-52)1216.5 (9.7e-112)1098.9 (1.1e-92)
L-VLDL-TG2941150.8 (1.3e-101)1213.6 (7e-112)1262.6 (5.2e-120)1162.8 (1.5e-103)
XL-VLDL-L2941196 (5.4e-109)829.4 (1.6e-52)442 (4.9e-08)423.6 (1.1e-06)
XL-VLDL-P2941265.9 (1.4e-120)1180.9 (1.6e-106)1202.2 (5.2e-110)982.1 (5.4e-75)
XL-VLDL-PL2961199.1 (6.9e-109)874.2 (1.9e-58)421.2 (2.3e-06)405.6 (2.3e-05)
XL-VLDL-TG2961184.3 (1.8e-106)828.6 (5.9e-52)430.8 (4.9e-07)430.1 (5.5e-07)
XXL-VLDL-L3041119.2 (1.2e-93)1041.9 (1.6e-81)900.9 (2e-60)699.6 (3.2e-33)
XXL-VLDL-P3031148 (1.7e-98)876.4 (4e-57)382.2 (0.0013)366 (0.0076)
XXL-VLDL-PL3031203 (2.1e-107)775.1 (4e-43)438.1 (5.8e-07)376.5 (0.0025)
XXL-VLDL-TG3031183 (3.7e-104)881.8 (6.6e-58)393.7 (0.00034)372.7 (0.0039)
LDL/IDL traits
LDL-C2931198.7 (9.6e-110)938.8 (1.1e-68)1060.2 (2.1e-87)917.6 (1.5e-65)
LDL-D2961325.2 (6.7e-130)747.9 (5.9e-41)879.1 (3.7e-59)1163.5 (4.6e-103)
S-LDL-C2961195.3 (2.9e-108)706 (1.6e-35)1426 (4.1e-147)686.4 (4.8e-33)
S-LDL-L2961054.7 (1.1e-85)608 (1e-23)1519.6 (2.2e-163)586.4 (2.5e-21)
S-LDL-P297852.9 (3.6e-55)438.7 (1.6e-07)954.7 (4.5e-70)440.1 (1.3e-07)
M-LDL-C2961210.9 (8e-111)396.2 (8.6e-05)409 (1.4e-05)398.9 (6e-05)
M-LDL-CE2951204.3 (4.8e-110)350.8 (0.014)361.7 (0.0048)351.3 (0.013)
M-LDL-L2961212 (5.3e-111)370 (0.0022)392.3 (0.00015)371.6 (0.0019)
M-LDL-P2971125.4 (1.2e-96)623.9 (2.3e-25)911.4 (1.3e-63)582.4 (9.6e-21)
M-LDL-PL2991172.5 (1.2e-103)399.3 (9.1e-05)434.9 (4.5e-07)396.2 (0.00014)
L-LDL-C3001174.6 (1.1e-103)325.5 (0.15)325.5 (0.15)325.5 (0.15)
L-LDL-CE2991179.5 (9e-105)769.8 (3e-43)902.5 (7.7e-62)743.8 (8.4e-40)
L-LDL-FC2951161 (5.8e-103)322.4 (0.13)323.2 (0.12)322.3 (0.13)
L-LDL-L3001172.3 (2.6e-103)336.9 (0.07)349.6 (0.026)340.3 (0.055)
L-LDL-P3001185.4 (2e-105)352.1 (0.021)378.4 (0.0014)355.4 (0.015)
L-LDL-PL2961155.2 (9.8e-102)343.2 (0.031)360.1 (0.0063)344.5 (0.027)
IDL-C2961181.7 (4.9e-106)426.5 (9.8e-07)427.6 (8.3e-07)427.7 (8.1e-07)
IDL-FC2981096.5 (9.9e-92)986.9 (1.1e-74)1075.8 (1.9e-88)975.4 (6.1e-73)
IDL-L2961176.1 (4e-105)516.7 (3.3e-14)531 (1.4e-15)521.4 (1.2e-14)
IDL-P2971094.8 (9.5e-92)910.9 (1.5e-63)1103.9 (3.5e-93)890.2 (1.6e-60)
IDL-PL2971107.8 (8.3e-94)798.9 (1.3e-47)931.6 (1.3e-66)785.6 (8.6e-46)
IDL-TG3021060.8 (5.4e-85)1052.1 (1.2e-83)1092.6 (5.6e-90)1118.3 (4.7e-94)
HDL traits
HDL-C298318.7 (0.2)336.3 (0.063)329.1 (0.1)318.6 (0.2)
HDL-D300637.4 (1.9e-26)1156.6 (9.1e-101)2305.2 (1.3e-305)1183.8 (3.5e-105)
S-HDL-L2991597.7 (4.8e-176)1222.5 (8.2e-112)1916.4 (1.5e-233)1057 (3.1e-85)
S-HDL-P2991666.8 (2.5e-188)1249.4 (2.9e-116)2146.5 (3.4e-276)1103.3 (1.6e-92)
S-HDL-TG299899 (2.5e-61)464.9 (2.4e-09)464.5 (2.6e-09)457.6 (9.2e-09)
M-HDL-C2991145.2 (3.2e-99)768.2 (4.9e-43)951.8 (4e-69)786.8 (1.5e-45)
M-HDL-CE2991201.9 (2e-108)1183.9 (1.7e-105)2139.7 (6.4e-275)843.9 (1.9e-53)
M-HDL-FC298881.1 (5.6e-59)1252 (5.5e-117)1989.1 (2.4e-247)660.1 (1.8e-29)
M-HDL-L2991059 (1.5e-85)766.4 (8.7e-43)920.6 (1.7e-64)672.5 (8.6e-31)
M-HDL-P298990.2 (3.5e-75)760.4 (3.4e-42)1027.6 (6.2e-81)613.7 (4.7e-24)
M-HDL-PL295929.5 (8.3e-67)763.9 (2.7e-43)1057.2 (2.3e-86)588.3 (1.1e-21)
L-HDL-C299579.3 (4.1e-20)623.2 (5.7e-25)639.6 (7.3e-27)617.8 (2.3e-24)
L-HDL-CE299612.2 (1e-23)650.7 (3.6e-28)690.4 (5.5e-33)644 (2.2e-27)
L-HDL-FC308581.7 (4.4e-19)857.5 (2.6e-53)1213.3 (1.4e-107)915.8 (1.3e-61)
L-HDL-L299655.9 (8.7e-29)747.7 (2.6e-40)670.7 (1.4e-30)713.2 (7.5e-36)
L-HDL-P298591.3 (1.5e-21)934 (9.9e-67)1269.7 (6.2e-120)956.8 (3.9e-70)
L-HDL-PL299580 (3.4e-20)863.5 (3.3e-56)1262.4 (2.1e-118)891.8 (2.8e-60)
XL-HDL-C298475.3 (2.7e-10)734 (1e-38)976.1 (4.9e-73)554 (1.3e-17)
XL-HDL-CE299472.9 (5.4e-10)736.9 (6.7e-39)1117.4 (9e-95)517.5 (6.5e-14)
XL-HDL-FC295527.8 (2.1e-15)1182.8 (1.6e-106)2169.4 (3.1e-282)677.3 (4.3e-32)
XL-HDL-L298555.2 (9.6e-18)701.2 (1.6e-34)1014 (7.9e-79)775.3 (3.4e-44)
XL-HDL-P300578.9 (6.3e-20)744.5 (1.1e-39)1015.5 (1.6e-78)751.3 (1.4e-40)
XL-HDL-PL306604.9 (7.8e-22)1153.9 (1.4e-98)1899 (1.5e-227)909.3 (3.7e-61)
XL-HDL-TG300702.2 (2.8e-34)779.8 (2.2e-44)1140.8 (3.2e-98)1399.2 (3.7e-141)
Appendix 4—table 1
List of SNPs associated with M-HDL-P.
SNPChrGeneS-HDL-PM-HDL-PL-HDL-PXL-HDL-PHDL-CLDL-CTGCAD
rs112080041DOCK7-0.039 **-0.075 ***-0.015-0.002-0.015 **-0.050 ***-0.069 ***-0.012
rs48469131GALNT2-0.000-0.061 ***-0.062 ***-0.023 .-0.055 ***-0.006-0.044 ***-0.025 .
rs21262598LOC157273-0.066 ***-0.082 ***-0.063 **-0.025 .-0.075 ***-0.063 ***-0.016 .-0.004
rs20836378LPL-0.001-0.058 ***-0.092 ***-0.053 **-0.105 ***-0.008-0.108 ***-0.047 **
rs1046801715ALDH1A2/LIPC-0.096 ***-0.060 ***-0.209 ***-0.202 ***-0.118 ***-0.002-0.038 ***-0.013
rs24761616CETP-0.058 ***-0.121 ***-0.198 ***-0.129 ***-0.243 ***-0.055 ***-0.039 ***-0.044 **
rs194397318LIPG-0.022-0.108 ***-0.104 ***-0.078 ***-0.077 ***-0.024 **-0.009-0.016
rs73733719DOCK6-0.047 .-0.087 ***-0.081 **-0.058 *-0.056 ***-0.007-0.011-0.038 .
rs76944919APOE-0.016-0.078 ***-0.071 ***-0.015-0.064 ***-0.214 ***-0.042 ***-0.085 ***
rs767920PCIF1/PLTP-0.188 ***-0.071 ***-0.129 ***-0.152 ***-0.059 ***-0.009-0.051 ***-0.025 .
Appendix 4—table 2
List of SNPs associated with S-HDL-P.
SNPChrGeneS-HDL-PM-HDL-PL-HDL-PXL-HDL-PHDL-CLDL-CTGCAD
rs7800942GCKR-0.074 ***-0.034 *-0.04 **-0.034 *-0.011 .-0.021 **-0.110 ***-0.005
rs109354733ST3GAL6-AS1-0.052 ***-0.014-0.029 .-0.031 *-0.009 .-0.003-0.005-0.007
rs493636311SIK3-0.064 ***-0.046 **-0.019-0.006-0.034 **-0.018 .-0.043 ***-0.022
rs204308515ALDH1A2/LIPC-0.092 ***-0.056 ***-0.202 ***-0.197 ***-0.106 ***-0.003-0.033 ***-0.008
rs180058815ALDH1A2/LIPC-0.106 ***-0.050 **-0.215 ***-0.212 ***-0.114 ***-0.002-0.044 ***-0.015
rs28971416CETP-0.077 ***-0.122 ***-0.162 ***-0.102 ***-0.214 ***-0.036 ***-0.035 ***-0.012
rs606590420PLTP-0.171 ***-0.060 ***-0.127 ***-0.149 ***-0.052 ***-0.008-0.040 ***-0.022 .
Appendix 4—table 3
Tissue-specific gene expressions associated with the 4 discovered genetic markers in the GTEx project.
SNP.IdTypeGene.SymbolVariant.Idp valueEffectTissue
rs838880eQTLSCARB1chr12_124777047_C_T_b381.5E-08-0.20Cells - Cultured fibroblasts
rs838880sQTLSCARB1chr12_124777047_C_T_b384.1E-06-0.34Testis
rs737337sQTLDOCK6chr19_11236817_T_C_b383.8E-430.99Artery - Tibial
rs737337sQTLDOCK6chr19_11236817_T_C_b386.4E-350.93Adipose - Subcutaneous
rs737337sQTLDOCK6chr19_11236817_T_C_b386.4E-350.93Adipose - Subcutaneous
rs737337sQTLDOCK6chr19_11236817_T_C_b381.6E-270.95Esophagus - Muscularis
rs737337sQTLDOCK6chr19_11236817_T_C_b383.2E-201.10Colon - Sigmoid
rs737337sQTLDOCK6chr19_11236817_T_C_b381.1E-170.93Esophagus - Gastroesophageal Junction
rs737337sQTLDOCK6chr19_11236817_T_C_b381.8E-090.81Artery - Coronary
rs737337sQTLDOCK6chr19_11236817_T_C_b381.2E-07-0.49Thyroid
rs737337sQTLKANK2chr19_11236817_T_C_b384.4E-070.43Artery - Tibial
rs737337sQTLKANK2chr19_11236817_T_C_b383.5E-060.55Heart - Left Ventricle
rs2943641eQTLIRS1chr2_226229029_T_C_b381.4E-16-0.30Adipose - Subcutaneous
rs2943641eQTLIRS1chr2_226229029_T_C_b386.1E-12-0.23Adipose - Visceral (Omentum)
rs2943641eQTLRP11-395N3.2chr2_226229029_T_C_b383.5E-09-0.23Adipose - Subcutaneous
rs2943641eQTLRP11-395N3.1chr2_226229029_T_C_b382.1E-07-0.23Adipose - Subcutaneous
rs2943641eQTLRP11-395N3.2chr2_226229029_T_C_b382.3E-06-0.19Adipose - Visceral (Omentum)
rs6065904eQTLPLTPchr20_45906012_G_A_b384.4E-22-0.27Muscle - Skeletal
rs6065904eQTLPLTPchr20_45906012_G_A_b381.6E-16-0.27Adipose - Subcutaneous
rs6065904eQTLPLTPchr20_45906012_G_A_b381.2E-15-0.28Adipose - Visceral (Omentum)
rs6065904eQTLPLTPchr20_45906012_G_A_b383.2E-15-0.42Heart - Atrial Appendage
rs6065904eQTLPLTPchr20_45906012_G_A_b387.2E-14-0.25Artery - Tibial
rs6065904eQTLPLTPchr20_45906012_G_A_b381.8E-12-0.27Nerve - Tibial
rs6065904eQTLPLTPchr20_45906012_G_A_b387.3E-12-0.26Esophagus - Muscularis
rs6065904eQTLPLTPchr20_45906012_G_A_b382.0E-11-0.29Colon - Transverse
rs6065904eQTLPLTPchr20_45906012_G_A_b384.1E-11-0.32Colon - Sigmoid
rs6065904eQTLPLTPchr20_45906012_G_A_b381.2E-09-0.26Artery - Aorta
rs6065904eQTLPLTPchr20_45906012_G_A_b384.2E-09-0.29Heart - Left Ventricle
rs6065904eQTLPLTPchr20_45906012_G_A_b385.0E-09-0.22Thyroid
rs6065904eQTLPLTPchr20_45906012_G_A_b381.7E-08-0.29Stomach
rs6065904eQTLPLTPchr20_45906012_G_A_b384.3E-08-0.24Lung
rs6065904eQTLNEURL2chr20_45906012_G_A_b386.6E-08-0.26Adipose - Subcutaneous
rs6065904eQTLPLTPchr20_45906012_G_A_b386.8E-08-0.33Liver
rs6065904eQTLCTSAchr20_45906012_G_A_b384.0E-07-0.14Nerve - Tibial
rs6065904eQTLPLTPchr20_45906012_G_A_b385.3E-07-0.37Spleen
rs6065904eQTLNEURL2chr20_45906012_G_A_b385.6E-07-0.26Adipose - Visceral (Omentum)
rs6065904eQTLPLTPchr20_45906012_G_A_b388.9E-07-0.46Small Intestine - Terminal Ileum
rs6065904eQTLRP3-337O18.9chr20_45906012_G_A_b381.8E-06-0.22Adipose - Subcutaneous
rs6065904eQTLWFDC3chr20_45906012_G_A_b382.9E-06-0.31Nerve - Tibial
rs6065904eQTLDNTTIP1chr20_45906012_G_A_b383.1E-06-0.17Artery - Tibial
rs6065904eQTLWFDC3chr20_45906012_G_A_b384.5E-06-0.27Skin - Sun Exposed (Lower leg)
rs6065904eQTLSNX21chr20_45906012_G_A_b384.8E-06-0.15Esophagus - Muscularis
rs6065904eQTLWFDC3chr20_45906012_G_A_b388.9E-06-0.27Skin - Not Sun Exposed (Suprapubic)
rs6065904eQTLDNTTIP1chr20_45906012_G_A_b381.0E-05-0.14Nerve - Tibial
rs6065904eQTLPLTPchr20_45906012_G_A_b381.1E-05-0.27Prostate
rs6065904eQTLPLTPchr20_45906012_G_A_b381.3E-05-0.26Pituitary
rs6065904eQTLPLTPchr20_45906012_G_A_b381.4E-05-0.21Esophagus - Gastroesophageal Junction
rs6065904eQTLSNX21chr20_45906012_G_A_b381.5E-05-0.16Esophagus - Mucosa
rs6065904eQTLSNX21chr20_45906012_G_A_b381.7E-05-0.23Colon - Sigmoid
rs6065904eQTLSNX21chr20_45906012_G_A_b381.7E-05-0.17Thyroid
rs6065904eQTLPLTPchr20_45906012_G_A_b382.6E-05-0.21Breast - Mammary Tissue
rs6065904eQTLWFDC3chr20_45906012_G_A_b382.9E-05-0.23Artery - Tibial
rs6065904eQTLNEURL2chr20_45906012_G_A_b383.2E-05-0.21Thyroid
rs6065904eQTLPLTPchr20_45906012_G_A_b383.7E-05-0.17Testis
rs6065904eQTLCTSAchr20_45906012_G_A_b384.4E-05-0.11Skin - Not Sun Exposed (Suprapubic)
rs6065904eQTLWFDC3chr20_45906012_G_A_b385.8E-05-0.23Muscle - Skeletal
rs6065904eQTLNEURL2chr20_45906012_G_A_b388.2E-05-0.27Heart - Atrial Appendage
rs6065904eQTLSNX21chr20_45906012_G_A_b388.4E-05-0.17Artery - Aorta
rs6065904eQTLNEURL2chr20_45906012_G_A_b389.5E-05-0.24Artery - Aorta
rs6065904eQTLWFDC3chr20_45906012_G_A_b389.5E-05-0.31Artery - Aorta
rs6065904eQTLRP3-337O18.9chr20_45906012_G_A_b389.5E-05-0.29Heart - Atrial Appendage
rs6065904eQTLPLTPchr20_45906012_G_A_b381.2E-04-0.15Skin - Sun Exposed (Lower leg)
rs6065904eQTLWFDC13chr20_45906012_G_A_b381.5E-040.28Esophagus - Muscularis
rs6065904eQTLDNTTIP1chr20_45906012_G_A_b382.1E-04-0.12Cells - Cultured fibroblasts
rs6065904sQTLZNF335chr20_45906012_G_A_b383.3E-11-0.65Testis
rs6065904sQTLACOT8chr20_45906012_G_A_b381.3E-090.58Heart - Left Ventricle
rs6065904sQTLPLTPchr20_45906012_G_A_b384.5E-08-0.32Whole Blood
rs6065904sQTLPLTPchr20_45906012_G_A_b384.8E-080.53Spleen
rs6065904sQTLACOT8chr20_45906012_G_A_b381.3E-070.42Esophagus - Mucosa
rs6065904sQTLACOT8chr20_45906012_G_A_b382.6E-070.49Heart - Atrial Appendage
rs6065904sQTLCTSAchr20_45906012_G_A_b381.0E-06-0.41Artery - Aorta
rs6065904sQTLACOT8chr20_45906012_G_A_b381.2E-060.33Nerve - Tibial
rs6065904sQTLACOT8chr20_45906012_G_A_b381.2E-060.67Brain - Spinal cord (cervical c-1)
rs6065904sQTLTNNC2chr20_45906012_G_A_b382.1E-060.54Brain - Cerebellum
rs6065904sQTLACOT8chr20_45906012_G_A_b382.1E-060.54Brain - Cerebellum
rs6065904sQTLWFDC3chr20_45906012_G_A_b385.5E-060.23Skin - Sun Exposed (Lower leg)
rs6065904sQTLWFDC3chr20_45906012_G_A_b389.4E-06-0.28Skin - Not Sun Exposed (Suprapubic)

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