Plasma lipid levels and risk of primary open angle glaucoma: a genetic study using Mendelian randomization

BMC Ophthalmology

Mengqiao Xu¹  Dawei Luo¹  Minwen Zhou¹  Shengguo Li²  Jundong Zhu³  Weitao Song⁴ 

[1] Department of Ophthalmology, Shanghai First People’s Hospital, School of Medicine, Shanghai JiaoTong University, 100 Haining Road, 200080, Shanghai, China;Shanghai Key Laboratory of Fundus Disease, Shanghai, China;Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, China;Department of Ophthalmology, the First People’s Hospital of Chenzhou, Southern Medical University, Chenzhou, China;Eye Center of Xiangya Hospital, Central South University; Hunan Key Laboratory of Ophthalmology, Changsha, China;

关键词: Primary open angle glaucoma;    Plasma lipid;    Mendelian randomization;   

DOI  :  10.1186/s12886-020-01661-0

来源: Springer

【 摘 要 】

BackgroundThe 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 Mendelian randomization (MR) analysis, whether plasma lipid concentrations are causally associated with the risk of POAG.MethodsTwo-sample 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 single-nucleotide polymorphisms (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.ResultsUsing 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.ConclusionsThe 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.

【 授权许可】

CC BY