Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis

Figures

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  Fig 1. Manhattan plots showing findings from the GWAS of lipoprotein lipid-related traits in the UKBB. Horizontal dotted line illustrates the Y-axis value conventionally used to denote a SNP that reaches statistical significance in the GWAS, i.e., at P < 5 × 10−8. GWAS, genome-wide association study; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SNP, single nucleotide polymorphism; UKBB, UK Biobank.

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  Fig 2. Characteristics of genetic instruments developed for lipoprotein lipid-related traits. (A) Overlap of SNPs and (B) associations with lipids and apolipoproteins. In Panel A, SNPs are grouped according to whether they associate with only the primary lipid-related trait of interest or whether they associate with other traits, based on P < 5 × 10−8. Panel B displays the associations of genetic instruments with lipid-related traits using the inverse variance weighting approach. Whilst we note the potential for overfitting of estimates displayed in Panel B, we present these data for illustrative purposes; the MR estimates presented in Fig 3 use a two-sample approach (with no overlapping data). CI, confidence interval; HDL, high-density lipoprotein; LDL, low-density lipoprotein; MR, Mendelian randomisation; NA, not applicable; SD, standard deviation; SNP, single nucleotide polymorphism.

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  Fig 3. Univariable and multivariable MR of so-called (A) atherogenic and (B) protective lipoprotein lipids and apolipoproteins and risk of CHD. In both (A) and (B), univariable MR estimates were derived using the inverse variance weighted approach. For a more comprehensive repertoire of estimates derived from univariable MR approaches, please see S2 Fig. CHD, coronary heart disease; CI, confidence interval; HDL, high-density lipoprotein; LDL, low-density lipoprotein; MR, Mendelian randomisation; SD, standard deviation; SNP, single nucleotide polymorphism.