Plasma Lipid Levels and Risk of Primary Open Angle Glaucoma: A Genetic Study Using Mendelian Randomization

Abstract

Background: The causal effects of plasma lipid concentrations and the risk of primary open angle glaucoma (POAG) are still unclear. Thus, the purpose of this study was to identify, applying a two-sample MR analysis, whether plasma lipid concentrations are causally associated with the risk of POAG.Methods Two-sample Mendelian randomization (MR) analysis of data from a genome-wide association study (GWAS) was performed to investigate the causal role of plasma lipid levels and POAG. A total of 185 independent SNPs associated with plasma lipid levels were selected as instrumental variables (IVs). The SNPs were obtained from a meta-analysis of GWAS based on 188,577 European-ancestry individuals for MR analyses. Association with POAG for the SNPs was obtained from a GWAS conducted among the United Kingdom (UK) Biobank study participants with a total of 463,010 European-ancestry individuals. Four MR methods (inverse variance weighted [IVW], weighted mode, weighted median, and MR-Egger regression) were applied to obtain the overall causal estimate for multiple, instrumental SNPs.Results Using the IVW analysis method, no evidence was found to support a causal association between plasma LDL-C level and POAG risk (β=-0.00026; 95% CI=-0.00062, 0.00011; P=0.165) with no significant heterogeneity among SNPs. The overall causal estimate between plasma LDL-C level and POAG was consistent using the other three MR methods. Using the four MR methods, no evidence of an association between plasma HDL-C (β=0.00023; 95% CI=-0.00015, 0.00061; P=0.238; IVW method) or TG levels (β=-0.00028; 95% CI=-0.00071, 0.00015; P=0.206; IVW method) and POAG risk was found. Sensitivity analyses did not reveal any sign of directional pleiotropy.Conclusions The present study did not find any evidence for a causal association between plasma lipid levels and POAG risk. Further research is needed to elucidate the potential biological mechanisms to provide a reasonable interpretation for these results.