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

Figures
Tables
Additional files

11 figures, 15 tables and 1 additional file

Figures

Figure 1

Download asset Open asset

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.

Figure 2

Download asset Open asset

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.

Figure 3

Download asset Open asset

Genetic markers for HDL size (with risk alleles) and their associations with various lipid traits.

Appendix 2—figure 1

Download asset Open asset

Genetic correlations computed using the Davis et al., 2017 GWAS summary dataset.

Appendix 2—figure 2

Download asset Open asset

Genetic correlations computed using the Kettunen et al., 2016 GWAS summary dataset.

Appendix 2—figure 3

Download asset Open asset

Genetic correlations computed by meta-analyzing the results in Appendix 2—figures 1 and 2.

Appendix 3—figure 1

Download asset Open asset

Mendelian randomization results for the 27 lipoprotein measurements selected in phenotypic screening.

Appendix 4—figure 1

Download asset Open asset

Diagnostic plots for S-HDL-P (selection: Davis; exposure: Kettunen; outcome: UK Biobank).

Appendix 4—figure 2

Download asset Open asset

Diagnostic plots for M-HDL-P (selection: Davis; exposure: Kettunen; outcome: UK Biobank).

Appendix 4—figure 3

Download asset Open asset

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

Download asset Open asset

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.

Phenotype	Dataset name	PubMed ID	Population	Sample size	Sample overlap with other datasets	URL to summary dataset
Traditional lipid traits	GERA	29507422 Hoffmann et al., 2018	Multi-ethnic	94,674		ftp://ftp.ebi.ac.uk/pub/databases/gwas/summary_statistics/
	GLGC	24097068 Willer et al., 2013	European	188,578	Kettunen, CARDIoGRAMplusC4D	http://csg.sph.umich.edu/abecasis/public/lipids2013/
Lipoprotein subfraction traits	Davis	29084231 Davis et al., 2017	Finnish	8372		http://csg.sph.umich.edu/boehnke/public/metsim-2017-lipoproteins/
	Kettunen	27005778 Kettunen et al., 2016	European	24,925	GLGC, CARDIoGRAMplusC4D	http://www.computationalmedicine.fi/data#NMR_GWAS
Heart disease traits	CARDIoGRAMplusC4D (CAD)	26343387 Nikpay et al., 2015	Mostly European	185,000	GLGC, Kettunen	http://www.cardiogramplusc4d.org/data-downloads/
	CARDIoGRAMplusC4D + UK Biobank (CAD)	28714975 Nelson et al., 2017	Mostly European
	UK Biobank (MI)	Interim round two release Abbott et al., 2018	European	360,420		http://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.

Trait	Effect of TG	Effect of LDL-C	Effect of HDL-C	Effect of subfraction/particle size
None	0.19 [0.09,0.29]	0.38 [0.33,0.44]	−0.053 [-0.13,0.03]
M-HDL-P	0.37 [0.22,0.52]	0.39 [0.32,0.45]	0.30 [0.08,0.52]	−0.69 [-1.09,–0.3]
S-HDL-P	0.23 [0.12,0.33]	0.45 [0.38,0.52]	−0.11 [-0.2,–0.02]	−0.33 [-0.52,–0.15]
HDL-D	0.11 [0.00,0.22]	0.42 [0.36,0.49]	−0.44 [-0.69,–0.2]	0.33 [0.11,0.56]
	Effect of TG	Effect of ApoB	Effect of ApoA1	Effect of Subfraction/Particle size
None	0.05 [-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-P	0.07 [-0.03,0.17]	0.53 [0.41,0.65]	−0.13 [-0.25,–0.02]	−0.24 [-0.40,–0.08]
HDL-D	0.06 [-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).

Trait	Description	Davis
VLDL traits and total triglycerides
TG	Total triglycerides
VLDL-D	VLDL diameter
XS-VLDL-L	Total lipids in very small VLDL	NA
XS-VLDL-P	Concentration of very small VLDL particles
XS-VLDL-PL	Phospholipids in very small VLDL
XS-VLDL-TG	Triglycerides in very small VLDL
S-VLDL-C	Total cholesterol in small VLDL
S-VLDL-FC	Free cholesterol in small VLDL
S-VLDL-L	Total lipids in small VLDL	NA
S-VLDL-P	Concentration of small VLDL particles
S-VLDL-PL	Phospholipids in small VLDL
S-VLDL-TG	Triglycerides in small VLDL
M-VLDL-C	Total cholesterol in medium VLDL
M-VLDL-CE	Cholesterol esters in medium VLDL
M-VLDL-FC	Free cholesterol in medium VLDL
M-VLDL-L	Total lipids in medium VLDL	NA
M-VLDL-P	Concentration of medium VLDL particles
M-VLDL-PL	Phospholipids in medium VLDL
M-VLDL-TG	Triglycerides in medium VLDL
L-VLDL-C	Total cholesterol in large VLDL
L-VLDL-CE	Cholesterol esters in large VLDL
L-VLDL-FC	Free cholesterol in large VLDL
L-VLDL-L	Total lipids in large VLDL	NA
L-VLDL-P	Concentration of large VLDL particles
L-VLDL-PL	Phospholipids in large VLDL
L-VLDL-TG	Triglycerides in large VLDL
XL-VLDL-L	Total lipids in very large VLDL	NA
XL-VLDL-P	Concentration of very large VLDL particles
XL-VLDL-PL	Phospholipids in very large VLDL
XL-VLDL-TG	Triglycerides in very large VLDL
XXL-VLDL-L	Total lipids in chylomicrons and extremely very large VLDL	NA
XXL-VLDL-P	Concentration of chylomicrons and extremely very large VLDL particles
XXL-VLDL-PL	Phospholipids in chylomicrons and extremely very large
XXL-VLDL-TG	Triglycerides in chylomicrons and extremely very large
LDL and IDL traits
LDL-C	Total cholesterol in LDL
ApoB	Apolipoprotein B
LDL-D	LDL diameter
S-LDL-C	Total cholesterol in small LDL
S-LDL-L	Total lipids in small LDL	NA
S-LDL-P	Phospholipids in small LDL
M-LDL-C	Total cholesterol in medium LDL
M-LDL-CE	Cholesterol esters in medium LDL
M-LDL-L	Total lipids in medium LDL	NA
M-LDL-P	Concentration of medium LDL particles
M-LDL-PL	Phospholipids in medium LDL
L-LDL-C	Total cholesterol in large LDL
L-LDL-CE	Cholesterol esters in large LDL
L-LDL-FC	Free cholesterol in large LDL
L-LDL-L	Total lipids in large LDL	NA
L-LDL-P	Concentration of large LDL particles
L-LDL-PL	Phospholipids in large LDL
IDL-C	Total cholesterol in IDL
IDL-FC	Free cholesterol in IDL
IDL-L	Total lipids in IDL	NA
IDL-P	Concentration of IDL particles
IDL-PL	Phospholipids in IDL
IDL-TG	Triglycerides in IDL
HDL traits
HDL-C	Total cholesterol in HDL
ApoA1	Apolipoprotein A1
HDL-D	HDL diameter
S-HDL-L	Total lipids in small HDL	NA
S-HDL-P	Concentration of small HDL particles
S-HDL-TG	Triglycerides in small HDL
M-HDL-C	Total cholesterol in medium HDL
M-HDL-CE	Cholesterol esters in medium HDL
M-HDL-FC	Free cholesterol in medium HDL
M-HDL-L	Total lipids in medium HDL	NA
M-HDL-P	Concentration of medium HDL particles
M-HDL-PL	Phospholipids in medium HDL
L-HDL-C	Total cholesterol in large HDL
L-HDL-CE	Cholesterol esters in large HDL
L-HDL-FC	Free cholesterol in large HDL
L-HDL-L	Total lipids in large HDL	NA
L-HDL-P	Concentration of large HDL particles
L-HDL-PL	Phospholipids in large HDL
XL-HDL-C	Total cholesterol in very large HDL
XL-HDL-CE	Cholesterol esters in very large HDL
XL-HDL-FC	Free cholesterol in very large HDL
XL-HDL-L	Total lipids in very large HDL	NA
XL-HDL-P	Concentration of very large HDL particles
XL-HDL-PL	Phospholipids in very large HDL
XL-HDL-TG	Triglycerides 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.

Trait	ApoA1	ApoB	HDL-C	LDL-C	TG
S-HDL-L	0.31 (0.28)	0.34 (0.25)	0.13 (0.26)	0.27 (0.3)	0.2 (0.22)
S-HDL-P	0.36 (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-C	0.65 (0.14)	−0.18 (0.2)	0.81 (0.09)	−0.09 (0.25)	−0.34 (0.17)
M-HDL-CE	0.68 (0.14)	−0.23 (0.21)	0.57 (0.12)	−0.24 (0.24)	−0.32 (0.18)
M-HDL-FC	0.67 (0.12)	−0.08 (0.21)	0.83 (0.08)	0.04 (0.24)	−0.28 (0.18)
M-HDL-L	0.71 (0.15)	0.02 (0.27)	0.52 (0.17)	−0.03 (0.29)	−0.19 (0.25)
M-HDL-P	0.75 (0.12)	0.15 (0.23)	0.46 (0.14)	0.08 (0.26)	0 (0.19)
M-HDL-PL	0.69 (0.13)	0.04 (0.22)	0.65 (0.11)	0.02 (0.25)	−0.04 (0.19)
L-HDL-C	0.76 (0.11)	−0.42 (0.13)	0.95 (0.02)	−0.1 (0.18)	−0.62 (0.09)
L-HDL-CE	0.82 (0.1)	−0.4 (0.12)	0.93 (0.04)	−0.16 (0.17)	−0.62 (0.09)
L-HDL-FC	0.66 (0.12)	−0.46 (0.13)	0.92 (0.03)	−0.13 (0.18)	−0.7 (0.08)
L-HDL-L	0.81 (0.11)	−0.29 (0.15)	0.74 (0.07)	−0.15 (0.18)	−0.56 (0.12)
L-HDL-P	0.79 (0.09)	−0.35 (0.13)	0.82 (0.05)	−0.12 (0.16)	−0.61 (0.09)
L-HDL-PL	0.77 (0.09)	−0.34 (0.13)	0.79 (0.05)	−0.12 (0.17)	−0.61 (0.09)
XL-HDL-C	0.75 (0.16)	−0.25 (0.19)	0.9 (0.1)	0.4 (0.27)	−0.63 (0.13)
XL-HDL-CE	0.82 (0.16)	−0.17 (0.19)	0.82 (0.09)	0.41 (0.27)	−0.54 (0.12)
XL-HDL-FC	0.72 (0.14)	−0.37 (0.18)	0.94 (0.08)	0.17 (0.23)	−0.71 (0.11)
XL-HDL-L	0.93 (0.16)	−0.08 (0.25)	0.68 (0.14)	0.1 (0.27)	−0.35 (0.2)
XL-HDL-P	0.81 (0.13)	−0.32 (0.16)	0.86 (0.08)	0.17 (0.21)	−0.69 (0.11)
XL-HDL-PL	0.76 (0.12)	−0.41 (0.15)	0.83 (0.07)	−0.09 (0.18)	−0.7 (0.09)
XL-HDL-TG	0.72 (0.13)	0.49 (0.17)	0.33 (0.13)	0.13 (0.26)	0.3 (0.15)
HDL-D	0.7 (0.11)	−0.36 (0.13)	0.8 (0.06)	−0.08 (0.17)	−0.64 (0.09)
IDL-C	0.38 (0.21)	0.58 (0.19)	0.07 (0.19)	0.8 (0.14)	0.39 (0.17)
IDL-FC	0.23 (0.2)	0.78 (0.12)	−0.05 (0.17)	0.61 (0.19)	0.44 (0.15)
IDL-L	0.38 (0.23)	0.65 (0.18)	0.05 (0.2)	0.64 (0.2)	0.47 (0.17)
IDL-P	0.31 (0.2)	0.66 (0.14)	−0.04 (0.17)	0.82 (0.13)	0.49 (0.14)
IDL-PL	0.25 (0.23)	0.83 (0.1)	−0.12 (0.19)	0.7 (0.19)	0.64 (0.15)
IDL-TG	0.22 (0.18)	0.82 (0.08)	−0.2 (0.13)	0.56 (0.15)	0.67 (0.08)
S-LDL-C	0.11 (0.28)	0.66 (0.18)	−0.16 (0.22)	0.44 (0.34)	0.58 (0.14)
S-LDL-L	0.26 (0.23)	0.66 (0.17)	−0.06 (0.21)	0.62 (0.21)	0.58 (0.13)
S-LDL-P	0.34 (0.2)	0.68 (0.15)	−0.02 (0.19)	0.63 (0.18)	0.58 (0.13)
M-LDL-C	0.15 (0.26)	0.63 (0.18)	0.22 (0.22)	0.87 (0.08)	0.13 (0.23)
M-LDL-CE	0.3 (0.23)	0.61 (0.2)	0.05 (0.21)	0.65 (0.2)	0.45 (0.16)
M-LDL-L	0.29 (0.22)	0.63 (0.18)	0.01 (0.21)	0.66 (0.19)	0.5 (0.15)
M-LDL-P	0.29 (0.23)	0.63 (0.18)	−0.01 (0.21)	0.65 (0.21)	0.51 (0.15)
M-LDL-PL	0.2 (0.24)	0.69 (0.16)	0.11 (0.2)	0.89 (0.06)	0.18 (0.22)
L-LDL-C	0.25 (0.24)	0.58 (0.21)	0.25 (0.22)	0.68 (0.19)	0.23 (0.21)
L-LDL-CE	0.3 (0.23)	0.58 (0.22)	0.05 (0.21)	0.65 (0.21)	0.41 (0.17)
L-LDL-FC	0.31 (0.24)	0.57 (0.22)	0.33 (0.23)	0.7 (0.18)	0.13 (0.23)
L-LDL-L	0.31 (0.23)	0.61 (0.2)	0.04 (0.21)	0.65 (0.21)	0.44 (0.17)
L-LDL-P	0.31 (0.23)	0.63 (0.19)	0.02 (0.21)	0.65 (0.21)	0.47 (0.16)
L-LDL-PL	0.27 (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-L	0.25 (0.23)	0.8 (0.08)	−0.2 (0.17)	0.61 (0.14)	0.73 (0.09)
XS-VLDL-P	0.17 (0.18)	0.83 (0.07)	−0.26 (0.13)	0.57 (0.13)	0.71 (0.07)
XS-VLDL-PL	0.21 (0.19)	0.78 (0.09)	−0.15 (0.15)	0.74 (0.14)	0.57 (0.11)
XS-VLDL-TG	0.06 (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-C	0.01 (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-CE	0.01 (0.19)	0.78 (0.08)	−0.43 (0.12)	0.5 (0.15)	0.9 (0.03)
M-VLDL-FC	0 (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-PL	0.03 (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-CE	0 (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-PL	0.01 (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-P	0.17 (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 design	Selection	Exposure	Outcome	Reported in
Univariable(traditional selection)	GERA	Davis	CARDIoGRAMplusC4D	Appendix 3—table 2–4
	GERA	Davis	UK Biobank	Appendix 3—table 2–4
	GERA	Kettunen	UK Biobank	Appendix 3—table 2–4
	GLGC	Davis	UK Biobank	Appendix 3—table 2–4
Univariable(subfraction selection)	Davis	Kettunen	UK Biobank	Figure 2; Appendix 3—figure 1 and Appendix 3—table 2–4
Univariable(subfraction selection)	Kettunen	Davis	UK Biobank	Appendix 3—figure 1 and Appendix 3—table 2–4
Multivariable	Davis, GERA	Kettunen, GLGC	CARDIoGRAMplusC4D+ UK Biobank	Figure 2, Table 2; Appendix 3—figure 1 and Appendix 3—table 2–4

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
Screening	GERA	GERA	GERA	GLGC	Davis	Kettunen	GERA + Davis	GERA + Davis
Exposure	Davis	Davis	Kettunen	Davis	Kettunen	Davis	GLGC + Kettunen	GLGC + Kettunen
Outcome	CAD	UKB	UKB	UKB	UKB	UKB	CAD + UKB	CAD + UKB
Adjusted							HDL-C + LDL-C + TG	ApoA1 + ApoB + TG
VLDL traits
TG	0.258 (0.053)	0.296 (0.075)	NA	0.262 (0.06)	NA	0.289 (0.068)	NA	NA
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-L	NA	NA	0.368 (0.064)	NA	0.429 (0.059)	NA	0.132 (0.119)	0.084 (0.141)
XS-VLDL-P	0.17 (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-PL	0.191 (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-TG	0.201 (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-C	0.294 (0.06)	0.343 (0.076)	NA	0.322 (0.063)	NA	0.424 (0.094)	-1.035 (0.323)	-1.265 (0.568)
S-VLDL-FC	0.243 (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-L	NA	NA	0.356 (0.075)	NA	0.376 (0.072)	NA	-0.898 (0.28)	-1.629 (0.586)
S-VLDL-P	0.226 (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-PL	0.228 (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-TG	0.223 (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-C	0.253 (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-CE	0.248 (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-FC	0.245 (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-L	NA	NA	0.311 (0.079)	NA	0.358 (0.078)	NA	-1.878 (0.75)	-0.298 (0.098)
M-VLDL-P	0.25 (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-PL	0.248 (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-TG	0.205 (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-C	0.299 (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-CE	0.247 (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-FC	0.316 (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-L	NA	NA	0.36 (0.096)	NA	0.32 (0.102)	NA	-1.277 (0.313)	-0.532 (0.278)
L-VLDL-P	0.268 (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-PL	0.322 (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-TG	0.243 (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-L	NA	NA	0.289 (0.098)	NA	0.435 (0.14)	NA	-1.069 (0.203)	-0.577 (0.249)
XL-VLDL-P	0.27 (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-PL	0.446 (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-TG	0.294 (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-L	NA	NA	0.397 (0.108)	NA	0.312 (0.108)	NA	-1.355 (0.318)	-0.402 (0.144)
XXL-VLDL-P	0.308 (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-PL	0.338 (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-TG	0.384 (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-C	0.523 (0.043)	0.512 (0.053)	0.514 (0.042)	0.473 (0.055)	0.435 (0.048)	0.464 (0.048)	NA	0.319 (0.182)
ApoB	0.605 (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-D	0.271 (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-C	0.624 (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-L	NA	NA	0.561 (0.047)	NA	0.473 (0.057)	NA	-0.251 (0.145)	-0.005 (0.29)
S-LDL-P	0.621 (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-C	0.648 (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-CE	0.643 (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-L	NA	NA	0.559 (0.042)	NA	0.461 (0.049)	NA	-0.069 (0.191)	NaN
M-LDL-P	0.638 (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-PL	0.658 (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-C	0.627 (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-CE	0.638 (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-FC	0.609 (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-L	NA	NA	0.543 (0.04)	NA	0.468 (0.047)	NA	0.167 (0.273)	NaN
L-LDL-P	0.606 (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-PL	0.61 (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-C	0.596 (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-FC	0.586 (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-L	NA	NA	0.57 (0.043)	NA	0.494 (0.048)	NA	0.148 (0.175)	0.444 (0.328)
IDL-P	0.566 (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-PL	0.583 (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-TG	0.603 (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)	NA	NaN
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-L	NA	NA	-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-TG	0.354 (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-L	NA	NA	-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-L	NA	NA	-0.108 (0.05)	NA	-0.132 (0.052)	NA	0.457 (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-C	0.055 (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-CE	0.064 (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-FC	0.009 (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-L	NA	NA	0.073 (0.055)	NA	0.038 (0.058)	NA	0.358 (0.154)	0.481 (0.141)
XL-HDL-P	0.038 (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-PL	0.029 (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-TG	0.092 (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
Selection	GERA	GERA	GERA	GLGC	Davis	Kettunen
Exposure	Davis	Davis	Kettunen	Davis	Kettunen	Davis
Outcome	CAD	UKB	UKB	UKB	UKB	UKB
VLDL traits
TG	0.184 (0.051)	0.278 (0.076)	NA	0.309 (0.074)	NA	0.207 (0.064)
VLDL-D	0.044 (0.06)	0.052 (0.09)	0.038 (0.102)	0.118 (0.091)	-0.083 (0.16)	-0.083 (0.138)
XS-VLDL-L	NA	NA	0.353 (0.08)	NA	0.372 (0.083)	NA
XS-VLDL-P	0.162 (0.04)	0.256 (0.059)	0.352 (0.081)	0.273 (0.063)	0.374 (0.084)	0.373 (0.095)
XS-VLDL-PL	0.165 (0.046)	0.262 (0.069)	0.37 (0.088)	0.27 (0.075)	0.443 (0.048)	0.401 (0.07)
XS-VLDL-TG	0.179 (0.041)	0.277 (0.061)	0.362 (0.082)	0.288 (0.062)	0.335 (0.076)	0.314 (0.08)
S-VLDL-C	0.237 (0.053)	0.343 (0.08)	NA	0.339 (0.083)	NA	0.443 (0.116)
S-VLDL-FC	0.21 (0.05)	0.307 (0.076)	0.344 (0.098)	0.314 (0.076)	0.262 (0.122)	0.397 (0.116)
S-VLDL-L	NA	NA	0.318 (0.095)	NA	0.27 (0.106)	NA
S-VLDL-P	0.188 (0.049)	0.274 (0.074)	0.311 (0.093)	0.29 (0.072)	0.266 (0.103)	0.331 (0.142)
S-VLDL-PL	0.198 (0.048)	0.291 (0.072)	0.342 (0.091)	0.3 (0.072)	0.281 (0.089)	0.331 (0.125)
S-VLDL-TG	0.174 (0.051)	0.255 (0.076)	0.296 (0.094)	0.28 (0.073)	0.261 (0.102)	0.262 (0.093)
M-VLDL-C	0.188 (0.053)	0.265 (0.08)	0.305 (0.096)	0.287 (0.077)	0.361 (0.078)	0.32 (0.134)
M-VLDL-CE	0.203 (0.051)	0.285 (0.077)	0.32 (0.098)	0.295 (0.076)	0.264 (0.094)	0.291 (0.125)
M-VLDL-FC	0.165 (0.056)	0.233 (0.084)	0.292 (0.098)	0.27 (0.08)	0.3 (0.084)	0.303 (0.104)
M-VLDL-L	NA	NA	0.265 (0.104)	NA	0.357 (0.096)	NA
M-VLDL-P	0.153 (0.056)	0.214 (0.085)	0.276 (0.104)	0.258 (0.081)	0.322 (0.092)	0.268 (0.074)
M-VLDL-PL	0.163 (0.054)	0.23 (0.082)	0.296 (0.097)	0.266 (0.078)	0.302 (0.084)	0.289 (0.095)
M-VLDL-TG	0.14 (0.058)	0.196 (0.087)	0.268 (0.107)	0.247 (0.083)	0.327 (0.093)	0.245 (0.091)
L-VLDL-C	0.177 (0.06)	0.24 (0.091)	0.288 (0.106)	0.286 (0.089)	0.108 (0.223)	0.31 (0.084)
L-VLDL-CE	0.178 (0.057)	0.245 (0.087)	0.262 (0.105)	0.279 (0.086)	0.182 (0.187)	0.299 (0.077)
L-VLDL-FC	0.176 (0.063)	0.242 (0.094)	0.295 (0.108)	0.298 (0.091)	0.321 (0.101)	0.314 (0.082)
L-VLDL-L	NA	NA	0.291 (0.119)	NA	0.125 (0.232)	NA
L-VLDL-P	0.164 (0.062)	0.227 (0.093)	0.269 (0.108)	0.275 (0.09)	0.332 (0.127)	0.247 (0.076)
L-VLDL-PL	0.173 (0.061)	0.23 (0.092)	0.308 (0.115)	0.284 (0.088)	0.32 (0.127)	0.302 (0.079)
L-VLDL-TG	0.149 (0.063)	0.202 (0.095)	0.268 (0.118)	0.267 (0.092)	0.33 (0.131)	0.302 (0.08)
XL-VLDL-L	NA	NA	0.263 (0.123)	NA	0.365 (0.286)	NA
XL-VLDL-P	0.149 (0.063)	0.206 (0.095)	0.247 (0.122)	0.268 (0.096)	0.346 (0.28)	0.245 (0.077)
XL-VLDL-PL	0.176 (0.067)	0.243 (0.101)	0.292 (0.119)	0.323 (0.101)	0.333 (0.265)	0.344 (0.133)
XL-VLDL-TG	0.151 (0.066)	0.205 (0.1)	0.241 (0.12)	0.282 (0.1)	0.323 (0.272)	0.249 (0.081)
XXL-VLDL-L	NA	NA	0.356 (0.127)	NA	-0.165 (0.425)	NA
XXL-VLDL-P	0.228 (0.067)	0.35 (0.099)	0.372 (0.119)	0.376 (0.098)	-0.12 (0.389)	0.006 (0.153)
XXL-VLDL-PL	0.211 (0.07)	0.31 (0.105)	0.275 (0.125)	0.399 (0.107)	-0.145 (0.395)	0.071 (0.191)
XXL-VLDL-TG	0.221 (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-C	0.427 (0.049)	0.431 (0.054)	0.409 (0.077)	0.409 (0.054)	0.416 (0.099)	0.422 (0.063)
ApoB	0.506 (0.058)	0.525 (0.065)	0.474 (0.093)	0.473 (0.064)	0.636 (0.092)	0.569 (0.071)
LDL-D	0.217 (0.151)	0.423 (0.161)	1.121 (0.178)	0.271 (0.143)	0.309 (0.126)	0.211 (0.081)
S-LDL-C	0.481 (0.056)	0.467 (0.063)	0.445 (0.087)	0.438 (0.063)	0.44 (0.128)	0.436 (0.076)
S-LDL-L	NA	NA	0.44 (0.09)	NA	0.456 (0.132)	NA
S-LDL-P	0.501 (0.059)	0.494 (0.068)	0.449 (0.093)	0.472 (0.067)	0.49 (0.139)	0.588 (0.097)
M-LDL-C	0.475 (0.057)	0.457 (0.064)	0.426 (0.08)	0.427 (0.064)	0.418 (0.111)	0.436 (0.087)
M-LDL-CE	0.485 (0.058)	0.47 (0.065)	0.432 (0.078)	0.436 (0.064)	0.43 (0.107)	0.444 (0.085)
M-LDL-L	NA	NA	0.43 (0.08)	NA	0.43 (0.11)	NA
M-LDL-P	0.479 (0.057)	0.465 (0.064)	0.437 (0.081)	0.44 (0.064)	0.413 (0.122)	0.439 (0.093)
M-LDL-PL	0.5 (0.063)	0.49 (0.071)	0.437 (0.087)	0.464 (0.07)	0.443 (0.132)	0.497 (0.099)
L-LDL-C	0.449 (0.055)	0.436 (0.061)	0.432 (0.076)	0.411 (0.061)	0.409 (0.106)	0.417 (0.076)
L-LDL-CE	0.464 (0.056)	0.451 (0.062)	0.426 (0.075)	0.422 (0.062)	0.416 (0.102)	0.433 (0.077)
L-LDL-FC	0.425 (0.054)	0.411 (0.059)	0.424 (0.074)	0.393 (0.059)	0.387 (0.105)	0.394 (0.078)
L-LDL-L	NA	NA	0.427 (0.074)	NA	0.407 (0.103)	NA
L-LDL-P	0.448 (0.054)	0.442 (0.06)	0.435 (0.075)	0.421 (0.059)	0.413 (0.104)	0.424 (0.075)
L-LDL-PL	0.444 (0.056)	0.438 (0.061)	0.441 (0.078)	0.423 (0.061)	0.42 (0.109)	0.429 (0.076)
IDL-C	0.447 (0.055)	0.455 (0.059)	0.451 (0.075)	0.433 (0.06)	0.439 (0.085)	0.422 (0.07)
IDL-FC	0.429 (0.055)	0.439 (0.059)	0.468 (0.075)	0.414 (0.059)	0.431 (0.081)	0.402 (0.074)
IDL-L	NA	NA	0.467 (0.075)	NA	0.445 (0.085)	NA
IDL-P	0.443 (0.055)	0.467 (0.06)	0.48 (0.077)	0.45 (0.059)	0.446 (0.088)	0.426 (0.071)
IDL-PL	0.429 (0.055)	0.443 (0.059)	0.473 (0.078)	0.427 (0.059)	0.435 (0.092)	0.407 (0.069)
IDL-TG	0.461 (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-L	NA	NA	-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-TG	0.224 (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-L	NA	NA	-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-L	NA	NA	-0.106 (0.077)	NA	0.034 (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-C	0.03 (0.06)	-0.012 (0.084)	0.014 (0.099)	-0.05 (0.088)	-0.015 (0.165)	0.161 (0.101)
XL-HDL-CE	0.03 (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-L	NA	NA	0.001 (0.085)	NA	-0.009 (0.138)	NA
XL-HDL-P	0.015 (0.049)	-0.021 (0.067)	0.013 (0.088)	-0.042 (0.071)	0.103 (0.1)	0.135 (0.093)
XL-HDL-PL	0 (0.047)	-0.037 (0.065)	-0.026 (0.079)	-0.055 (0.069)	0.081 (0.088)	0.071 (0.069)
XL-HDL-TG	0.086 (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
Selection	GERA	GERA	GERA	GLGC	Davis	Kettunen
Exposure	Davis	Davis	Kettunen	Davis	Kettunen	Davis
Outcome	CAD	UKB	UKB	UKB	UKB	UKB
VLDL traits
TG	0.042 (0.055)	0.191 (0.072)	NA	0.228 (0.069)	NA	0.195 (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-L	NA	NA	0.312 (0.076)	NA	0.393 (0.078)	NA
XS-VLDL-P	0.101 (0.037)	0.23 (0.052)	0.303 (0.079)	0.229 (0.052)	0.409 (0.08)	0.253 (0.059)
XS-VLDL-PL	0.096 (0.039)	0.242 (0.059)	0.352 (0.087)	0.228 (0.06)	0.422 (0.065)	0.319 (0.062)
XS-VLDL-TG	0.125 (0.041)	0.266 (0.057)	0.287 (0.079)	0.221 (0.056)	0.361 (0.084)	0.306 (0.069)
S-VLDL-C	0.187 (0.059)	0.232 (0.075)	NA	0.256 (0.074)	NA	0.303 (0.094)
S-VLDL-FC	0.152 (0.057)	0.207 (0.069)	0.289 (0.093)	0.227 (0.069)	0.316 (0.109)	0.279 (0.077)
S-VLDL-L	NA	NA	0.282 (0.083)	NA	0.306 (0.099)	NA
S-VLDL-P	0.131 (0.057)	0.202 (0.069)	0.275 (0.085)	0.221 (0.062)	0.291 (0.093)	0.226 (0.078)
S-VLDL-PL	0.137 (0.053)	0.205 (0.067)	0.283 (0.083)	0.218 (0.062)	0.305 (0.092)	0.263 (0.075)
S-VLDL-TG	0.112 (0.057)	0.204 (0.067)	0.216 (0.088)	0.229 (0.064)	0.267 (0.099)	0.244 (0.073)
M-VLDL-C	0.12 (0.058)	0.2 (0.07)	0.255 (0.088)	0.213 (0.066)	0.303 (0.099)	0.224 (0.081)
M-VLDL-CE	0.144 (0.054)	0.207 (0.071)	0.262 (0.087)	0.207 (0.068)	0.301 (0.098)	0.209 (0.072)
M-VLDL-FC	0.081 (0.058)	0.188 (0.074)	0.221 (0.087)	0.218 (0.068)	0.272 (0.102)	0.231 (0.08)
M-VLDL-L	NA	NA	0.227 (0.095)	NA	0.275 (0.109)	NA
M-VLDL-P	0.047 (0.06)	0.191 (0.072)	0.221 (0.096)	0.226 (0.069)	0.31 (0.104)	0.257 (0.079)
M-VLDL-PL	0.103 (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-C	0.109 (0.068)	0.2 (0.078)	0.237 (0.093)	0.231 (0.075)	0.242 (0.122)	0.262 (0.088)
L-VLDL-CE	0.147 (0.063)	0.211 (0.079)	0.249 (0.09)	0.253 (0.073)	0.281 (0.11)	0.286 (0.081)
L-VLDL-FC	0.045 (0.065)	0.199 (0.085)	0.225 (0.093)	0.224 (0.077)	0.252 (0.125)	0.228 (0.089)
L-VLDL-L	NA	NA	0.243 (0.102)	NA	0.261 (0.122)	NA
L-VLDL-P	0.041 (0.064)	0.209 (0.082)	0.224 (0.092)	0.21 (0.079)	0.289 (0.122)	0.223 (0.086)
L-VLDL-PL	0.08 (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-L	NA	NA	0.262 (0.111)	NA	NA	NA
XL-VLDL-P	-0.026 (0.063)	0.207 (0.091)	0.289 (0.102)	0.192 (0.088)	NA	0.209 (0.101)
XL-VLDL-PL	-0.006 (0.067)	0.197 (0.094)	0.253 (0.094)	0.213 (0.088)	NA	0.24 (0.101)
XL-VLDL-TG	-0.026 (0.064)	0.214 (0.092)	0.229 (0.102)	0.191 (0.088)	NA	0.212 (0.099)
XXL-VLDL-L	NA	NA	0.316 (0.114)	NA	-0.156 (0.22)	NA
XXL-VLDL-P	0.091 (0.071)	0.236 (0.089)	0.267 (0.1)	0.263 (0.088)	-0.104 (0.173)	0.185 (0.098)
XXL-VLDL-PL	0.153 (0.082)	0.283 (0.096)	0.267 (0.11)	0.332 (0.095)	-0.139 (0.178)	0.126 (0.124)
XXL-VLDL-TG	0.126 (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-C	0.263 (0.053)	0.307 (0.066)	0.274 (0.05)	0.297 (0.063)	0.435 (0.072)	0.431 (0.067)
ApoB	0.365 (0.073)	0.472 (0.078)	0.381 (0.063)	0.375 (0.081)	0.624 (0.08)	0.565 (0.094)
LDL-D	0.306 (0.09)	0.413 (0.157)	0.467 (0.163)	0.271 (0.142)	0.294 (0.075)	0.193 (0.06)
S-LDL-C	0.271 (0.058)	0.342 (0.073)	0.343 (0.056)	0.273 (0.068)	0.498 (0.08)	0.274 (0.083)
S-LDL-L	NA	NA	0.354 (0.061)	NA	0.449 (0.081)	NA
S-LDL-P	0.355 (0.063)	0.366 (0.078)	0.397 (0.069)	0.329 (0.08)	0.49 (0.089)	0.581 (0.098)
M-LDL-C	0.283 (0.055)	0.313 (0.073)	0.299 (0.05)	0.244 (0.07)	0.474 (0.074)	0.297 (0.074)
M-LDL-CE	0.27 (0.055)	0.333 (0.077)	0.299 (0.051)	0.255 (0.071)	0.437 (0.081)	0.311 (0.077)
M-LDL-L	NA	NA	0.303 (0.053)	NA	0.432 (0.079)	NA
M-LDL-P	0.251 (0.057)	0.32 (0.071)	0.309 (0.054)	0.278 (0.07)	0.409 (0.072)	0.325 (0.078)
M-LDL-PL	0.343 (0.063)	0.337 (0.081)	0.316 (0.055)	0.318 (0.078)	0.457 (0.074)	0.353 (0.085)
L-LDL-C	0.251 (0.052)	0.29 (0.067)	0.303 (0.048)	0.231 (0.063)	0.45 (0.075)	0.309 (0.071)
L-LDL-CE	0.251 (0.054)	0.32 (0.068)	0.293 (0.052)	0.241 (0.066)	0.481 (0.074)	0.322 (0.077)
L-LDL-FC	0.251 (0.048)	0.214 (0.061)	0.301 (0.049)	0.214 (0.062)	0.427 (0.068)	0.289 (0.065)
L-LDL-L	NA	NA	0.289 (0.051)	NA	0.412 (0.07)	NA
L-LDL-P	0.281 (0.053)	0.321 (0.067)	0.29 (0.053)	0.244 (0.066)	0.42 (0.072)	0.351 (0.072)
L-LDL-PL	0.286 (0.05)	0.32 (0.067)	0.313 (0.052)	0.298 (0.065)	0.413 (0.074)	0.35 (0.076)
IDL-C	0.283 (0.056)	0.349 (0.068)	0.315 (0.053)	0.313 (0.07)	0.51 (0.072)	0.383 (0.068)
IDL-FC	0.283 (0.053)	0.334 (0.066)	0.337 (0.053)	0.314 (0.065)	0.422 (0.067)	0.367 (0.064)
IDL-L	NA	NA	0.329 (0.056)	NA	0.494 (0.069)	NA
IDL-P	0.331 (0.06)	0.44 (0.067)	0.343 (0.056)	0.371 (0.069)	0.463 (0.074)	0.328 (0.068)
IDL-PL	0.265 (0.055)	0.332 (0.066)	0.344 (0.056)	0.316 (0.066)	0.451 (0.072)	0.359 (0.066)
IDL-TG	0.233 (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)
ApoA1	0.094 (0.049)	-0.06 (0.076)	-0.069 (0.087)	-0.167 (0.07)	0.005 (0.083)	-0.051 (0.121)
HDL-D	0.079 (0.034)	0.062 (0.061)	0.102 (0.064)	0.088 (0.061)	0.099 (0.061)	0.096 (0.058)
S-HDL-L	NA	NA	-0.174 (0.113)	NA	NA	NA
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-TG	0.157 (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-L	NA	NA	-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-C	0.086 (0.037)	-0.009 (0.066)	0.031 (0.083)	-0.032 (0.08)	0.003 (0.09)	0.006 (0.068)
L-HDL-CE	0.086 (0.038)	-0.011 (0.067)	0.075 (0.077)	-0.037 (0.076)	0.015 (0.091)	-0.006 (0.068)
L-HDL-FC	0.09 (0.039)	-0.005 (0.067)	0.079 (0.081)	-0.019 (0.076)	0.041 (0.078)	0.027 (0.074)
L-HDL-L	NA	NA	0.074 (0.077)	NA	0.068 (0.084)	NA
L-HDL-P	0.081 (0.036)	0.046 (0.062)	0.075 (0.074)	-0.01 (0.066)	0.066 (0.07)	0.078 (0.064)
L-HDL-PL	0.084 (0.039)	0 (0.067)	0.051 (0.082)	-0.021 (0.071)	0.054 (0.075)	0.074 (0.071)
XL-HDL-C	0.163 (0.047)	0.122 (0.091)	0.136 (0.087)	0.132 (0.09)	0.02 (0.098)	0.161 (0.096)
XL-HDL-CE	0.139 (0.044)	0.106 (0.088)	0.122 (0.09)	0.148 (0.085)	0.038 (0.091)	0.336 (0.092)
XL-HDL-FC	0.135 (0.048)	0.065 (0.079)	0.133 (0.081)	0.027 (0.077)	0.159 (0.079)	0.052 (0.086)
XL-HDL-L	NA	NA	0.119 (0.075)	NA	0.023 (0.078)	NA
XL-HDL-P	0.115 (0.035)	0.087 (0.07)	0.12 (0.073)	0.129 (0.067)	0.16 (0.071)	0.15 (0.073)
XL-HDL-PL	0.101 (0.037)	0.064 (0.07)	0.11 (0.072)	0.121 (0.069)	0.141 (0.069)	0.088 (0.065)
XL-HDL-TG	0.074 (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).

Trait	HDL-C	LDL-C	TG	Subfraction
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-P	0.063 (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
ApoA1	0.345 (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-TG	0.002 (0.145)	0.314 (0.156)	-0.007 (0.469)	0.253 (0.637)
M-HDL-C	0.179 (0.097)	0.36 (0.038)	0.147 (0.054)	-0.508 (0.165)
M-HDL-CE	0.167 (0.087)	0.319 (0.036)	0.166 (0.055)	-0.487 (0.157)
M-HDL-FC	0.339 (0.141)	0.436 (0.04)	0.247 (0.059)	-0.649 (0.225)
M-HDL-L	0.27 (0.108)	0.362 (0.032)	0.299 (0.063)	-0.606 (0.188)
M-HDL-P	0.302 (0.112)	0.386 (0.033)	0.371 (0.075)	-0.694 (0.204)
M-HDL-PL	0.311 (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).

Trait	ApoA1	ApoB	TG	Subfraction
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-C	0.091 (0.084)	0.459 (0.101)	-0.1 (0.083)	-0.442 (0.143)
M-HDL-CE	0.09 (0.078)	0.291 (0.083)	0.082 (0.05)	-0.413 (0.137)
M-HDL-FC	0.148 (0.11)	0.378 (0.063)	0.066 (0.049)	-0.408 (0.166)
M-HDL-L	0.133 (0.091)	0.491 (0.097)	-0.029 (0.086)	-0.485 (0.155)
M-HDL-P	0.129 (0.097)	0.501 (0.097)	-0.004 (0.09)	-0.472 (0.166)
M-HDL-PL	0.162 (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.

Trait	DF	HDL-C	LDL-C	TG	Subfraction
VLDL traits
VLDL-D	432	7640.8 (0)	1918.9 (7.9e-186)	877.6 (1.4e-32)	840.2 (1.6e-28)
XS-VLDL-L	436	7983.9 (0)	1104.9 (1.1e-59)	1935.8 (2.2e-187)	926 (1.9e-37)
XS-VLDL-P	436	7927.8 (0)	1066.6 (1.1e-54)	1814 (4.8e-167)	893.6 (9.6e-34)
XS-VLDL-PL	435	8291.5 (0)	968.1 (1.4e-42)	2771.5 (0)	849.8 (4.3e-29)
XS-VLDL-TG	431	7549.8 (0)	894.4 (1.3e-34)	739.5 (1.3e-18)	682.5 (1.2e-13)
S-VLDL-C	429	8598.1 (0)	652.6 (1.7e-11)	1220.7 (4.6e-77)	541.3 (0.00018)
S-VLDL-FC	434	7861.2 (0)	576 (5.4e-06)	519.4 (0.003)	507.9 (0.0082)
S-VLDL-L	438	7105.3 (0)	626 (8.5e-09)	525.2 (0.0026)	514.3 (0.0069)
S-VLDL-P	438	6686.5 (0)	616.5 (3.6e-08)	515.6 (0.0061)	507.3 (0.012)
S-VLDL-PL	437	7589.1 (0)	702.8 (1e-14)	591.5 (1.1e-06)	555.1 (0.00011)
S-VLDL-TG	437	7658.7 (0)	612.7 (5.3e-08)	498.9 (0.021)	494.5 (0.03)
M-VLDL-C	432	9167.8 (0)	740.8 (1.3e-18)	558.9 (3.5e-05)	551.5 (8.3e-05)
M-VLDL-CE	432	8055.2 (0)	705.9 (1.6e-15)	556.6 (4.6e-05)	539.7 (0.00031)
M-VLDL-FC	436	8272.8 (0)	814.8 (2.7e-25)	528.3 (0.0016)	519.1 (0.0037)
M-VLDL-L	429	7109.2 (0)	1269.2 (5.5e-84)	532.6 (0.00047)	515.9 (0.0025)
M-VLDL-P	436	8260.7 (0)	2059.5 (2.1e-208)	527.5 (0.0017)	516.8 (0.0046)
M-VLDL-PL	435	6849.2 (0)	599.6 (2.6e-07)	496.8 (0.021)	493.5 (0.027)
M-VLDL-TG	436	6123.7 (0)	9854.8 (0)	532.3 (0.0011)	521 (0.0031)
L-VLDL-C	435	8617.2 (0)	8966 (0)	654.7 (4.3e-11)	561.5 (3.9e-05)
L-VLDL-CE	434	6636.6 (0)	11134 (0)	581.6 (2.6e-06)	539.5 (0.00041)
L-VLDL-FC	431	7779.6 (0)	6691 (0)	595.1 (2.5e-07)	562.7 (1.9e-05)
L-VLDL-L	434	8104.9 (0)	5191.4 (0)	560.3 (3.9e-05)	548.6 (0.00015)
L-VLDL-P	435	2308 (5.1e-252)	10360.3 (0)	545.4 (0.00024)	537.9 (0.00054)
L-VLDL-PL	430	8155.4 (0)	1310.8 (8.6e-90)	491.8 (0.021)	489.7 (0.024)
L-VLDL-TG	438	8581.8 (0)	4800.1 (0)	569.1 (2.3e-05)	559.2 (7.5e-05)
XL-VLDL-L	437	8686.8 (0)	8322.2 (0)	674.7 (1.9e-12)	620.2 (1.7e-08)
XL-VLDL-P	431	8550.2 (0)	2459.4 (2e-280)	608.3 (3.6e-08)	588.6 (6.3e-07)
XL-VLDL-PL	431	7478.2 (0)	5042.5 (0)	613.3 (1.7e-08)	591.6 (4.1e-07)
XL-VLDL-TG	433	8237.3 (0)	9628.9 (0)	651.8 (4.6e-11)	618.3 (1.1e-08)
XXL-VLDL-L	439	8476.2 (0)	10436.4 (0)	652.9 (1.3e-10)	570.7 (2.2e-05)
XXL-VLDL-P	437	1291.3 (2.8e-85)	9987.4 (0)	540.3 (0.00053)	529.5 (0.0016)
XXL-VLDL-PL	436	9631.8 (0)	11287.1 (0)	641.6 (4.8e-10)	595.5 (5.3e-07)
XXL-VLDL-TG	429	7809.4 (0)	9476.4 (0)	595.6 (1.7e-07)	564 (1.2e-05)
LDL/IDL traits
ApoB	435	9220.8 (0)	550.1 (0.00014)	1809.7 (1.2e-166)	535.1 (0.00072)
LDL-D	429	2909.2 (0)	3918.8 (0)	2706 (0)	1426.1 (2.9e-107)
S-LDL-C	431	8189.7 (0)	569.8 (7.8e-06)	4880.9 (0)	564.1 (1.6e-05)
S-LDL-L	435	8403.8 (0)	574.4 (7.8e-06)	3931.2 (0)	564.3 (2.7e-05)
S-LDL-P	431	7371.4 (0)	547.1 (0.00012)	3144.7 (0)	537.9 (0.00034)
M-LDL-C	430	9723.7 (0)	570.9 (5.8e-06)	6568.6 (0)	562.9 (1.6e-05)
M-LDL-CE	432	8442.1 (0)	558.3 (3.8e-05)	5773.6 (0)	549.1 (0.00011)
M-LDL-L	430	8801.7 (0)	555.4 (4e-05)	5176.1 (0)	548.2 (9.5e-05)
M-LDL-P	429	8798.9 (0)	541.6 (0.00018)	5049.7 (0)	535.2 (0.00035)
M-LDL-PL	436	7981.7 (0)	573.9 (9.6e-06)	4304.8 (0)	558.9 (6e-05)
L-LDL-C	432	8865.2 (0)	567.7 (1.2e-05)	6179.8 (0)	567 (1.3e-05)
L-LDL-CE	433	8464.3 (0)	558.7 (4.1e-05)	5731.3 (0)	555.6 (5.9e-05)
L-LDL-FC	431	7481.1 (0)	580.6 (1.9e-06)	6760.8 (0)	580.2 (2e-06)
L-LDL-L	433	8486.8 (0)	604.5 (8.9e-08)	5755.8 (0)	601.8 (1.3e-07)
L-LDL-P	434	8310.7 (0)	592.1 (6.3e-07)	5553.3 (0)	584.9 (1.7e-06)
L-LDL-PL	435	8341.4 (0)	588.5 (1.2e-06)	5327.8 (0)	577.4 (5.3e-06)
IDL-C	434	7873.9 (0)	645.5 (1.7e-10)	6336 (0)	642.1 (2.9e-10)
IDL-FC	432	8036 (0)	729.5 (1.4e-17)	6630.5 (0)	725.6 (3e-17)
IDL-L	434	7869.8 (0)	694.5 (2.4e-14)	5198.3 (0)	689 (7e-14)
IDL-P	436	9660.5 (0)	736.7 (9e-18)	5002 (0)	726.6 (7.1e-17)
IDL-PL	431	8432.6 (0)	680.6 (1.7e-13)	5023 (0)	677.4 (3e-13)
IDL-TG	436	7741.2 (0)	1077.5 (4.2e-56)	1992.9 (4.9e-197)	931.6 (4.4e-38)
HDL traits
ApoA1	434	494.1 (0.024)	511.5 (0.006)	932.1 (1.8e-38)	492 (0.028)
HDL-D	438	783.5 (6.6e-22)	8500 (0)	5713.2 (0)	860.1 (9.4e-30)
S-HDL-L	438	3067.3 (0)	4414.6 (0)	3763.2 (0)	882.2 (3.7e-32)
S-HDL-P	438	2592.4 (1.1e-301)	7652.1 (0)	3097.3 (0)	951.1 (4.9e-40)
S-HDL-TG	425	896.9 (6.9e-36)	641.3 (5.2e-11)	540.1 (0.00013)	523 (8e-04)
M-HDL-C	437	957.6 (5.5e-41)	10172.4 (0)	4875.5 (0)	628.3 (4.9e-09)
M-HDL-CE	434	955.3 (3.2e-41)	1383.1 (1.7e-99)	4355.4 (0)	648.3 (1e-10)
M-HDL-FC	432	759.4 (2.4e-20)	2989.1 (0)	3512.2 (0)	538.2 (0.00037)
M-HDL-L	435	914.2 (3e-36)	11535.3 (0)	2327.7 (1.7e-255)	570.3 (1.3e-05)
M-HDL-P	434	997.6 (2.3e-46)	10709.6 (0)	1942.9 (3.2e-189)	561.3 (3.4e-05)
M-HDL-PL	434	977.8 (6.3e-44)	9439.9 (0)	2566 (1.8e-298)	581.3 (2.7e-06)
L-HDL-C	434	580 (3.2e-06)	1257.1 (4.4e-81)	4502.7 (0)	604.3 (1.1e-07)
L-HDL-CE	434	549 (0.00014)	930.2 (3e-38)	5517.2 (0)	557.2 (5.6e-05)
L-HDL-FC	441	627.6 (1.2e-08)	8415.3 (0)	3594 (0)	658.4 (7.9e-11)
L-HDL-L	434	603.6 (1.2e-07)	6743.8 (0)	5314.7 (0)	623.7 (5.7e-09)
L-HDL-P	432	601.1 (1.2e-07)	7769.3 (0)	6024.6 (0)	633.2 (8.6e-10)
L-HDL-PL	434	584.5 (1.8e-06)	9935.5 (0)	3544.3 (0)	611.3 (3.8e-08)
XL-HDL-C	430	732.9 (3.9e-18)	10426.6 (0)	2077.7 (1.4e-213)	686.9 (4e-14)
XL-HDL-CE	430	771.4 (9.3e-22)	8564.4 (0)	2457 (2.2e-280)	711.4 (3.3e-16)
XL-HDL-FC	432	761.8 (1.4e-20)	11265.2 (0)	2549.4 (3.1e-296)	770.9 (1.9e-21)
XL-HDL-L	429	767.6 (1.6e-21)	11490.7 (0)	2355.7 (1.2e-262)	784.6 (3.4e-23)
XL-HDL-P	433	724.9 (4.6e-17)	11372.5 (0)	2539.9 (3.9e-294)	798.5 (4.8e-24)
XL-HDL-PL	443	809.7 (7.8e-24)	10093.1 (0)	5762 (0)	895.4 (7.5e-33)
XL-HDL-TG	432	1849.1 (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.

Trait	DF	ApoA1	ApoB	TG	Subfraction
VLDL traits
VLDL-D	297	1194.1 (9.1e-108)	550 (2.4e-17)	573.7 (8.2e-20)	606.7 (2.1e-23)
XS-VLDL-L	295	1185.1 (6.7e-107)	927 (2e-66)	1151.3 (2.2e-101)	887.9 (1.1e-60)
XS-VLDL-P	295	1194.9 (1.7e-108)	900 (1.9e-62)	895.5 (8.7e-62)	826.7 (6.4e-52)
XS-VLDL-PL	296	1148.5 (1.2e-100)	973.9 (3.2e-73)	2104.2 (1.4e-269)	961.4 (2.5e-71)
XS-VLDL-TG	302	1263.7 (1.1e-117)	757.9 (4.7e-41)	1308.1 (4.4e-125)	976.5 (4.6e-72)
S-VLDL-C	290	988.8 (4.4e-77)	394 (4.5e-05)	459.8 (7.8e-10)	402.6 (1.3e-05)
S-VLDL-FC	296	1092 (1.4e-91)	904 (8.6e-63)	1238.7 (2.1e-115)	1010.4 (8.1e-79)
S-VLDL-L	301	1107.9 (1.1e-92)	412.3 (2.1e-05)	420.8 (5.9e-06)	384.7 (0.00078)
S-VLDL-P	301	1116.6 (4.6e-94)	424.8 (3.3e-06)	401.3 (9.4e-05)	380.6 (0.0013)
S-VLDL-PL	299	1096 (2.3e-91)	428.9 (1.2e-06)	446 (7.1e-08)	432.1 (7.1e-07)
S-VLDL-TG	300	1152.4 (4.3e-100)	908.5 (1.8e-62)	1453.4 (1.8e-150)	1303.1 (7.1e-125)
M-VLDL-C	298	1171.2 (1e-103)	824 (7.3e-51)	1480 (8.9e-156)	1212.5 (1.8e-110)
M-VLDL-CE	298	1185.4 (4.9e-106)	564.4 (1.1e-18)	468.9 (9.2e-10)	431.6 (6.3e-07)
M-VLDL-FC	298	1190.4 (7.4e-107)	899.8 (1.1e-61)	415.2 (8.1e-06)	398.8 (8.4e-05)
M-VLDL-L	298	1144.1 (2.4e-99)	869.8 (2.4e-57)	1381 (1e-138)	1237.4 (1.4e-114)
M-VLDL-P	297	1121.3 (5.7e-96)	821.1 (1.1e-50)	1250.5 (4.6e-117)	1206.7 (8.1e-110)
M-VLDL-PL	298	1149.9 (2.8e-100)	843.2 (1.5e-53)	1391.8 (1.5e-140)	1226.3 (9.8e-113)
M-VLDL-TG	296	1187.4 (5.8e-107)	717.3 (5.8e-37)	366.3 (0.0033)	360.6 (0.006)
L-VLDL-C	295	1196.5 (9.1e-109)	820 (5.6e-51)	462.5 (1.5e-09)	376.9 (0.00088)
L-VLDL-CE	302	1183.1 (1.8e-104)	844.6 (7.4e-53)	541.8 (7.2e-16)	441.7 (2.6e-07)
L-VLDL-FC	295	1172.3 (8.2e-105)	851.6 (1.9e-55)	460.8 (2.1e-09)	406.2 (1.8e-05)
L-VLDL-L	295	1163.6 (2.2e-103)	797 (8.8e-48)	406.5 (1.7e-05)	391.5 (0.00014)
L-VLDL-P	293	1160.2 (2e-103)	809.5 (5.9e-50)	420.2 (1.5e-06)	407.9 (1e-05)
L-VLDL-PL	296	1292 (2.6e-124)	833.4 (1.3e-52)	1216.5 (9.7e-112)	1098.9 (1.1e-92)
L-VLDL-TG	294	1150.8 (1.3e-101)	1213.6 (7e-112)	1262.6 (5.2e-120)	1162.8 (1.5e-103)
XL-VLDL-L	294	1196 (5.4e-109)	829.4 (1.6e-52)	442 (4.9e-08)	423.6 (1.1e-06)
XL-VLDL-P	294	1265.9 (1.4e-120)	1180.9 (1.6e-106)	1202.2 (5.2e-110)	982.1 (5.4e-75)
XL-VLDL-PL	296	1199.1 (6.9e-109)	874.2 (1.9e-58)	421.2 (2.3e-06)	405.6 (2.3e-05)
XL-VLDL-TG	296	1184.3 (1.8e-106)	828.6 (5.9e-52)	430.8 (4.9e-07)	430.1 (5.5e-07)
XXL-VLDL-L	304	1119.2 (1.2e-93)	1041.9 (1.6e-81)	900.9 (2e-60)	699.6 (3.2e-33)
XXL-VLDL-P	303	1148 (1.7e-98)	876.4 (4e-57)	382.2 (0.0013)	366 (0.0076)
XXL-VLDL-PL	303	1203 (2.1e-107)	775.1 (4e-43)	438.1 (5.8e-07)	376.5 (0.0025)
XXL-VLDL-TG	303	1183 (3.7e-104)	881.8 (6.6e-58)	393.7 (0.00034)	372.7 (0.0039)
LDL/IDL traits
LDL-C	293	1198.7 (9.6e-110)	938.8 (1.1e-68)	1060.2 (2.1e-87)	917.6 (1.5e-65)
LDL-D	296	1325.2 (6.7e-130)	747.9 (5.9e-41)	879.1 (3.7e-59)	1163.5 (4.6e-103)
S-LDL-C	296	1195.3 (2.9e-108)	706 (1.6e-35)	1426 (4.1e-147)	686.4 (4.8e-33)
S-LDL-L	296	1054.7 (1.1e-85)	608 (1e-23)	1519.6 (2.2e-163)	586.4 (2.5e-21)
S-LDL-P	297	852.9 (3.6e-55)	438.7 (1.6e-07)	954.7 (4.5e-70)	440.1 (1.3e-07)
M-LDL-C	296	1210.9 (8e-111)	396.2 (8.6e-05)	409 (1.4e-05)	398.9 (6e-05)
M-LDL-CE	295	1204.3 (4.8e-110)	350.8 (0.014)	361.7 (0.0048)	351.3 (0.013)
M-LDL-L	296	1212 (5.3e-111)	370 (0.0022)	392.3 (0.00015)	371.6 (0.0019)
M-LDL-P	297	1125.4 (1.2e-96)	623.9 (2.3e-25)	911.4 (1.3e-63)	582.4 (9.6e-21)
M-LDL-PL	299	1172.5 (1.2e-103)	399.3 (9.1e-05)	434.9 (4.5e-07)	396.2 (0.00014)
L-LDL-C	300	1174.6 (1.1e-103)	325.5 (0.15)	325.5 (0.15)	325.5 (0.15)
L-LDL-CE	299	1179.5 (9e-105)	769.8 (3e-43)	902.5 (7.7e-62)	743.8 (8.4e-40)
L-LDL-FC	295	1161 (5.8e-103)	322.4 (0.13)	323.2 (0.12)	322.3 (0.13)
L-LDL-L	300	1172.3 (2.6e-103)	336.9 (0.07)	349.6 (0.026)	340.3 (0.055)
L-LDL-P	300	1185.4 (2e-105)	352.1 (0.021)	378.4 (0.0014)	355.4 (0.015)
L-LDL-PL	296	1155.2 (9.8e-102)	343.2 (0.031)	360.1 (0.0063)	344.5 (0.027)
IDL-C	296	1181.7 (4.9e-106)	426.5 (9.8e-07)	427.6 (8.3e-07)	427.7 (8.1e-07)
IDL-FC	298	1096.5 (9.9e-92)	986.9 (1.1e-74)	1075.8 (1.9e-88)	975.4 (6.1e-73)
IDL-L	296	1176.1 (4e-105)	516.7 (3.3e-14)	531 (1.4e-15)	521.4 (1.2e-14)
IDL-P	297	1094.8 (9.5e-92)	910.9 (1.5e-63)	1103.9 (3.5e-93)	890.2 (1.6e-60)
IDL-PL	297	1107.8 (8.3e-94)	798.9 (1.3e-47)	931.6 (1.3e-66)	785.6 (8.6e-46)
IDL-TG	302	1060.8 (5.4e-85)	1052.1 (1.2e-83)	1092.6 (5.6e-90)	1118.3 (4.7e-94)
HDL traits
HDL-C	298	318.7 (0.2)	336.3 (0.063)	329.1 (0.1)	318.6 (0.2)
HDL-D	300	637.4 (1.9e-26)	1156.6 (9.1e-101)	2305.2 (1.3e-305)	1183.8 (3.5e-105)
S-HDL-L	299	1597.7 (4.8e-176)	1222.5 (8.2e-112)	1916.4 (1.5e-233)	1057 (3.1e-85)
S-HDL-P	299	1666.8 (2.5e-188)	1249.4 (2.9e-116)	2146.5 (3.4e-276)	1103.3 (1.6e-92)
S-HDL-TG	299	899 (2.5e-61)	464.9 (2.4e-09)	464.5 (2.6e-09)	457.6 (9.2e-09)
M-HDL-C	299	1145.2 (3.2e-99)	768.2 (4.9e-43)	951.8 (4e-69)	786.8 (1.5e-45)
M-HDL-CE	299	1201.9 (2e-108)	1183.9 (1.7e-105)	2139.7 (6.4e-275)	843.9 (1.9e-53)
M-HDL-FC	298	881.1 (5.6e-59)	1252 (5.5e-117)	1989.1 (2.4e-247)	660.1 (1.8e-29)
M-HDL-L	299	1059 (1.5e-85)	766.4 (8.7e-43)	920.6 (1.7e-64)	672.5 (8.6e-31)
M-HDL-P	298	990.2 (3.5e-75)	760.4 (3.4e-42)	1027.6 (6.2e-81)	613.7 (4.7e-24)
M-HDL-PL	295	929.5 (8.3e-67)	763.9 (2.7e-43)	1057.2 (2.3e-86)	588.3 (1.1e-21)
L-HDL-C	299	579.3 (4.1e-20)	623.2 (5.7e-25)	639.6 (7.3e-27)	617.8 (2.3e-24)
L-HDL-CE	299	612.2 (1e-23)	650.7 (3.6e-28)	690.4 (5.5e-33)	644 (2.2e-27)
L-HDL-FC	308	581.7 (4.4e-19)	857.5 (2.6e-53)	1213.3 (1.4e-107)	915.8 (1.3e-61)
L-HDL-L	299	655.9 (8.7e-29)	747.7 (2.6e-40)	670.7 (1.4e-30)	713.2 (7.5e-36)
L-HDL-P	298	591.3 (1.5e-21)	934 (9.9e-67)	1269.7 (6.2e-120)	956.8 (3.9e-70)
L-HDL-PL	299	580 (3.4e-20)	863.5 (3.3e-56)	1262.4 (2.1e-118)	891.8 (2.8e-60)
XL-HDL-C	298	475.3 (2.7e-10)	734 (1e-38)	976.1 (4.9e-73)	554 (1.3e-17)
XL-HDL-CE	299	472.9 (5.4e-10)	736.9 (6.7e-39)	1117.4 (9e-95)	517.5 (6.5e-14)
XL-HDL-FC	295	527.8 (2.1e-15)	1182.8 (1.6e-106)	2169.4 (3.1e-282)	677.3 (4.3e-32)
XL-HDL-L	298	555.2 (9.6e-18)	701.2 (1.6e-34)	1014 (7.9e-79)	775.3 (3.4e-44)
XL-HDL-P	300	578.9 (6.3e-20)	744.5 (1.1e-39)	1015.5 (1.6e-78)	751.3 (1.4e-40)
XL-HDL-PL	306	604.9 (7.8e-22)	1153.9 (1.4e-98)	1899 (1.5e-227)	909.3 (3.7e-61)
XL-HDL-TG	300	702.2 (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.

SNP	Chr	Gene	S-HDL-P	M-HDL-P	L-HDL-P	XL-HDL-P	HDL-C	LDL-C	TG	CAD
rs11208004	1	DOCK7	-0.039 **	-0.075 ***	-0.015	-0.002	-0.015 **	-0.050 ***	-0.069 ***	-0.012
rs4846913	1	GALNT2	-0.000	-0.061 ***	-0.062 ***	-0.023 .	-0.055 ***	-0.006	-0.044 ***	-0.025 .
rs2126259	8	LOC157273	-0.066 ***	-0.082 ***	-0.063 **	-0.025 .	-0.075 ***	-0.063 ***	-0.016 .	-0.004
rs2083637	8	LPL	-0.001	-0.058 ***	-0.092 ***	-0.053 **	-0.105 ***	-0.008	-0.108 ***	-0.047 **
rs10468017	15	ALDH1A2/LIPC	-0.096 ***	-0.060 ***	-0.209 ***	-0.202 ***	-0.118 ***	-0.002	-0.038 ***	-0.013
rs247616	16	CETP	-0.058 ***	-0.121 ***	-0.198 ***	-0.129 ***	-0.243 ***	-0.055 ***	-0.039 ***	-0.044 **
rs1943973	18	LIPG	-0.022	-0.108 ***	-0.104 ***	-0.078 ***	-0.077 ***	-0.024 **	-0.009	-0.016
rs737337	19	DOCK6	-0.047 .	-0.087 ***	-0.081 **	-0.058 *	-0.056 ***	-0.007	-0.011	-0.038 .
rs769449	19	APOE	-0.016	-0.078 ***	-0.071 ***	-0.015	-0.064 ***	-0.214 ***	-0.042 ***	-0.085 ***
rs7679	20	PCIF1/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.

SNP	Chr	Gene	S-HDL-P	M-HDL-P	L-HDL-P	XL-HDL-P	HDL-C	LDL-C	TG	CAD
rs780094	2	GCKR	-0.074 ***	-0.034 *	-0.04 **	-0.034 *	-0.011 .	-0.021 **	-0.110 ***	-0.005
rs10935473	3	ST3GAL6-AS1	-0.052 ***	-0.014	-0.029 .	-0.031 *	-0.009 .	-0.003	-0.005	-0.007
rs4936363	11	SIK3	-0.064 ***	-0.046 **	-0.019	-0.006	-0.034 **	-0.018 .	-0.043 ***	-0.022
rs2043085	15	ALDH1A2/LIPC	-0.092 ***	-0.056 ***	-0.202 ***	-0.197 ***	-0.106 ***	-0.003	-0.033 ***	-0.008
rs1800588	15	ALDH1A2/LIPC	-0.106 ***	-0.050 **	-0.215 ***	-0.212 ***	-0.114 ***	-0.002	-0.044 ***	-0.015
rs289714	16	CETP	-0.077 ***	-0.122 ***	-0.162 ***	-0.102 ***	-0.214 ***	-0.036 ***	-0.035 ***	-0.012
rs6065904	20	PLTP	-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.Id	Type	Gene.Symbol	Variant.Id	p value	Effect	Tissue
rs838880	eQTL	SCARB1	chr12_124777047_C_T_b38	1.5E-08	-0.20	Cells - Cultured fibroblasts
rs838880	sQTL	SCARB1	chr12_124777047_C_T_b38	4.1E-06	-0.34	Testis
rs737337	sQTL	DOCK6	chr19_11236817_T_C_b38	3.8E-43	0.99	Artery - Tibial
rs737337	sQTL	DOCK6	chr19_11236817_T_C_b38	6.4E-35	0.93	Adipose - Subcutaneous
rs737337	sQTL	DOCK6	chr19_11236817_T_C_b38	6.4E-35	0.93	Adipose - Subcutaneous
rs737337	sQTL	DOCK6	chr19_11236817_T_C_b38	1.6E-27	0.95	Esophagus - Muscularis
rs737337	sQTL	DOCK6	chr19_11236817_T_C_b38	3.2E-20	1.10	Colon - Sigmoid
rs737337	sQTL	DOCK6	chr19_11236817_T_C_b38	1.1E-17	0.93	Esophagus - Gastroesophageal Junction
rs737337	sQTL	DOCK6	chr19_11236817_T_C_b38	1.8E-09	0.81	Artery - Coronary
rs737337	sQTL	DOCK6	chr19_11236817_T_C_b38	1.2E-07	-0.49	Thyroid
rs737337	sQTL	KANK2	chr19_11236817_T_C_b38	4.4E-07	0.43	Artery - Tibial
rs737337	sQTL	KANK2	chr19_11236817_T_C_b38	3.5E-06	0.55	Heart - Left Ventricle
rs2943641	eQTL	IRS1	chr2_226229029_T_C_b38	1.4E-16	-0.30	Adipose - Subcutaneous
rs2943641	eQTL	IRS1	chr2_226229029_T_C_b38	6.1E-12	-0.23	Adipose - Visceral (Omentum)
rs2943641	eQTL	RP11-395N3.2	chr2_226229029_T_C_b38	3.5E-09	-0.23	Adipose - Subcutaneous
rs2943641	eQTL	RP11-395N3.1	chr2_226229029_T_C_b38	2.1E-07	-0.23	Adipose - Subcutaneous
rs2943641	eQTL	RP11-395N3.2	chr2_226229029_T_C_b38	2.3E-06	-0.19	Adipose - Visceral (Omentum)
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	4.4E-22	-0.27	Muscle - Skeletal
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	1.6E-16	-0.27	Adipose - Subcutaneous
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	1.2E-15	-0.28	Adipose - Visceral (Omentum)
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	3.2E-15	-0.42	Heart - Atrial Appendage
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	7.2E-14	-0.25	Artery - Tibial
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	1.8E-12	-0.27	Nerve - Tibial
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	7.3E-12	-0.26	Esophagus - Muscularis
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	2.0E-11	-0.29	Colon - Transverse
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	4.1E-11	-0.32	Colon - Sigmoid
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	1.2E-09	-0.26	Artery - Aorta
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	4.2E-09	-0.29	Heart - Left Ventricle
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	5.0E-09	-0.22	Thyroid
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	1.7E-08	-0.29	Stomach
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	4.3E-08	-0.24	Lung
rs6065904	eQTL	NEURL2	chr20_45906012_G_A_b38	6.6E-08	-0.26	Adipose - Subcutaneous
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	6.8E-08	-0.33	Liver
rs6065904	eQTL	CTSA	chr20_45906012_G_A_b38	4.0E-07	-0.14	Nerve - Tibial
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	5.3E-07	-0.37	Spleen
rs6065904	eQTL	NEURL2	chr20_45906012_G_A_b38	5.6E-07	-0.26	Adipose - Visceral (Omentum)
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	8.9E-07	-0.46	Small Intestine - Terminal Ileum
rs6065904	eQTL	RP3-337O18.9	chr20_45906012_G_A_b38	1.8E-06	-0.22	Adipose - Subcutaneous
rs6065904	eQTL	WFDC3	chr20_45906012_G_A_b38	2.9E-06	-0.31	Nerve - Tibial
rs6065904	eQTL	DNTTIP1	chr20_45906012_G_A_b38	3.1E-06	-0.17	Artery - Tibial
rs6065904	eQTL	WFDC3	chr20_45906012_G_A_b38	4.5E-06	-0.27	Skin - Sun Exposed (Lower leg)
rs6065904	eQTL	SNX21	chr20_45906012_G_A_b38	4.8E-06	-0.15	Esophagus - Muscularis
rs6065904	eQTL	WFDC3	chr20_45906012_G_A_b38	8.9E-06	-0.27	Skin - Not Sun Exposed (Suprapubic)
rs6065904	eQTL	DNTTIP1	chr20_45906012_G_A_b38	1.0E-05	-0.14	Nerve - Tibial
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	1.1E-05	-0.27	Prostate
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	1.3E-05	-0.26	Pituitary
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	1.4E-05	-0.21	Esophagus - Gastroesophageal Junction
rs6065904	eQTL	SNX21	chr20_45906012_G_A_b38	1.5E-05	-0.16	Esophagus - Mucosa
rs6065904	eQTL	SNX21	chr20_45906012_G_A_b38	1.7E-05	-0.23	Colon - Sigmoid
rs6065904	eQTL	SNX21	chr20_45906012_G_A_b38	1.7E-05	-0.17	Thyroid
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	2.6E-05	-0.21	Breast - Mammary Tissue
rs6065904	eQTL	WFDC3	chr20_45906012_G_A_b38	2.9E-05	-0.23	Artery - Tibial
rs6065904	eQTL	NEURL2	chr20_45906012_G_A_b38	3.2E-05	-0.21	Thyroid
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	3.7E-05	-0.17	Testis
rs6065904	eQTL	CTSA	chr20_45906012_G_A_b38	4.4E-05	-0.11	Skin - Not Sun Exposed (Suprapubic)
rs6065904	eQTL	WFDC3	chr20_45906012_G_A_b38	5.8E-05	-0.23	Muscle - Skeletal
rs6065904	eQTL	NEURL2	chr20_45906012_G_A_b38	8.2E-05	-0.27	Heart - Atrial Appendage
rs6065904	eQTL	SNX21	chr20_45906012_G_A_b38	8.4E-05	-0.17	Artery - Aorta
rs6065904	eQTL	NEURL2	chr20_45906012_G_A_b38	9.5E-05	-0.24	Artery - Aorta
rs6065904	eQTL	WFDC3	chr20_45906012_G_A_b38	9.5E-05	-0.31	Artery - Aorta
rs6065904	eQTL	RP3-337O18.9	chr20_45906012_G_A_b38	9.5E-05	-0.29	Heart - Atrial Appendage
rs6065904	eQTL	PLTP	chr20_45906012_G_A_b38	1.2E-04	-0.15	Skin - Sun Exposed (Lower leg)
rs6065904	eQTL	WFDC13	chr20_45906012_G_A_b38	1.5E-04	0.28	Esophagus - Muscularis
rs6065904	eQTL	DNTTIP1	chr20_45906012_G_A_b38	2.1E-04	-0.12	Cells - Cultured fibroblasts
rs6065904	sQTL	ZNF335	chr20_45906012_G_A_b38	3.3E-11	-0.65	Testis
rs6065904	sQTL	ACOT8	chr20_45906012_G_A_b38	1.3E-09	0.58	Heart - Left Ventricle
rs6065904	sQTL	PLTP	chr20_45906012_G_A_b38	4.5E-08	-0.32	Whole Blood
rs6065904	sQTL	PLTP	chr20_45906012_G_A_b38	4.8E-08	0.53	Spleen
rs6065904	sQTL	ACOT8	chr20_45906012_G_A_b38	1.3E-07	0.42	Esophagus - Mucosa
rs6065904	sQTL	ACOT8	chr20_45906012_G_A_b38	2.6E-07	0.49	Heart - Atrial Appendage
rs6065904	sQTL	CTSA	chr20_45906012_G_A_b38	1.0E-06	-0.41	Artery - Aorta
rs6065904	sQTL	ACOT8	chr20_45906012_G_A_b38	1.2E-06	0.33	Nerve - Tibial
rs6065904	sQTL	ACOT8	chr20_45906012_G_A_b38	1.2E-06	0.67	Brain - Spinal cord (cervical c-1)
rs6065904	sQTL	TNNC2	chr20_45906012_G_A_b38	2.1E-06	0.54	Brain - Cerebellum
rs6065904	sQTL	ACOT8	chr20_45906012_G_A_b38	2.1E-06	0.54	Brain - Cerebellum
rs6065904	sQTL	WFDC3	chr20_45906012_G_A_b38	5.5E-06	0.23	Skin - Sun Exposed (Lower leg)
rs6065904	sQTL	WFDC3	chr20_45906012_G_A_b38	9.4E-06	-0.28	Skin - Not Sun Exposed (Suprapubic)

Additional files

Transparent reporting form: https://cdn.elifesciences.org/articles/58361/elife-58361-transrepform-v2.docx
Download elife-58361-transrepform-v2.docx

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Article PDF

Open citations (links to open the citations from this article in various online reference manager services)

Mendeley

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

Qingyuan Zhao
Jingshu Wang
Zhen Miao
Nancy R Zhang
Sean Hennessy
Dylan S Small
Daniel J Rader

(2021)

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

eLife 10:e58361.

https://doi.org/10.7554/eLife.58361

Share this article

Cite this article

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

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.

Genetic correlations computed using the Davis et al., 2017 GWAS summary dataset.

Genetic correlations computed using the Kettunen et al., 2016 GWAS summary dataset.

Genetic correlations computed by meta-analyzing the results in Appendix 2—figures 1 and 2.

Mendelian randomization results for the 27 lipoprotein measurements selected in phenotypic screening.

Diagnostic plots for S-HDL-P (selection: Davis; exposure: Kettunen; outcome: UK Biobank).

Diagnostic plots for M-HDL-P (selection: Davis; exposure: Kettunen; outcome: UK Biobank).

Scatter-plots for S-HDL-P with the effects on CAD adjusted for LDL-C and TG.

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

Information about the GWAS summary datasets used in this article.

Results of some multivariable Mendelian randomization analyses.

All 82 traits included in this study and whether they are measured in the Kettunen and Davis GWAS (NA means not available).

Estimated genetic correlation (standard error) of the lipoprotein subfractions with the traditional lipid risk factors using the Davis GWAS.

Three-sample Mendelian randomization designs.

Mendelian randomization results using all selected SNPs (univariable MR using RAPS and multivariable MR using GRAPPLE).

Mendelian randomization results using genome-wide significant SNPs and inverse variance weighted (IVW) estimator.

Mendelian randomization results using genome-wide significant SNPs and the weighted median estimator.

Multivariable Mendelian randomization results (adjusted for HDL-C, LDL-C, and TG).

Multivariable Mendelian randomization results (adjusted for ApoA1, ApoB, and TG).

Modified Cochran’s Q-statistics (p-values) for the multivariable Mendelian randomization analyses (adjusted for HDL-C, LDL-C, and TG).

Modified Cochran’s Q-statistics (p-values) for the multivariable Mendelian randomization analyses (adjusted for ApoA1, ApoB, and TG).

List of SNPs associated with M-HDL-P.

List of SNPs associated with S-HDL-P.

Tissue-specific gene expressions associated with the 4 discovered genetic markers in the GTEx project.

Transparent reporting form

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)