Lipid-lowering drug targets and lung related diseases: a Mendelian randomization study

Figures & data

Figure 1. Study Overview and Mendelian Randomization Model. HMGCR, 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase; NPC1L1, Niemann-Pick C1-Like 1; PCSK9, Proprotein Convertase Subtilisin/Kexin type 9; LDLR, Low Density Lipoprotein Receptor; CETP, Cholesteryl Ester Transfer Protein; APOB, Apolipoprotein B; MR, Mendelian Randomization.

This is a study design roadmap that describes the selection of SNPS in relevant gene regions affecting LDL levels, and the use of Mendelian randomization to explore the relationship between lipid-lowering and six lung-related diseases, including small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), pulmonary edema (PE), and pneumonia.

Figure 2. Association between genetically proxied inhibition of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase (HMGCR), Niemann-Pick C1-Like 1 (NPC1L1), Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), Cholesteryl Ester Transfer Protein (CETP), low-density lipoprotein receptor (LDLR), Apolipoprotein B (APOB) with lung-related diseases (LRD) risk.

Forest plot of the relationship between six genes mimicking lipid-lowering drugs and six lung-related diseases, reporting detailed odds ratios as well as P-values for confidence intervals and significance.

Table 1. Inverse variance weighted estimates for positive control analyses.

Variable	OR	95%CI	P value	MR-egger intercept p value	Cochran’s Q test p value
APOB	0.715	0.635–0.806	3.46E-08	0.079	0.123
CETP	0.672	0.554–0.814	5.03E-05	0.335	0.815
HMGCR	0.683	0.568–0.82	4.63E-05	0.147	0.387
LDLR	0.522	0.466–0.584	1.22E-29	0.194	0.225
NPC1L	0.589	0.444–0.782	2.46E-04	0.464	0.843
PCSK9	0.601	0.521–0.693	2.59E-12	0.623	0.086

Data availability statement

This study utilized publicly available data from the GLGC (Global Lipids Genetics Consortium) at http://csg.sph.umich.edu/willer/public/lipids2013 and from the FinnGen consortium at https://www.finngen.fi/fi. Additional data supporting the findings of this study are available in figshare at https://doi.org/10.6084/m9.figshare.24885393.