The causal effects of plasma lipid levels and the risk of retinal vascular occlusion (RVO) have not been clearly identified, especially for high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C). Here, we try to identify these causal risk factors using a two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) were chosen as instrumental variables (IVs). We obtained genetic variants associated with lipid exposure at the genome-wide significance (P<5×10−8) level from a meta-analysis of GWAS from the Global Lipids Genetics Consortium (GLGC) based on 188,577 individuals of mostly European ancestry for MR analyses. Meanwhile, we used lipid GWAS from UK Biobank (UKB) with a sample size of 115,078 individuals as a supplement. We obtained genetic predictors of RVO from a FinnGen biobank study. We conducted both univariable and multivariable MR (MVMR) analyses to identify the causal effects of RVO. Although inverse variance weighted (IVW) was the primary method used for MR analyses, MR–Egger and weighted-median methods were used as supplements to IVW. We determined the heterogeneity of IVs using Cochrane’s Q test and I2, and used the MR–Egger intercept and MR-PRESSO Global test to detect horizontal pleiotropy. A leave-one-out sensitivity analysis was conducted by removing a single variant from the analysis. Genetically predicted increased HDL-C level was associated with decreased risk of RVO from GLGC [OR=0.806; 95% CI=(0.659, 0.986); P=0.036], which was consistent with UKB results [OR=0.766; 95% CI=(0.635, 0.925); P=0.005]. MVMR analysis for plasma lipids [adjusted OR=0.639; 95% CI=(0.411, 0.992); P=0.046] or diabetes [adjusted OR=0.81; 95% CI=(0.67, 0.979); P=0.029] suggested that low HDL-C may be an independent risk factor for RVO. However, there was no evidence to support a causal association between LDL-C {GLGC [adjusted OR=1.015; 95% CI=(0.408, 2.523); P=0.975], UKB [OR=1.115; 95% CI=(0.884, 1.407); P=0.359]}, total cholesterol {GLGC [adjusted OR=0.904; 95% CI=(0.307, 2.659); P=0.854], UKB [OR=1.047; 95% CI=(0.816, 1.344); P=0.716]} or triglycerides {GLGC [OR=1.103; 95% CI=(0.883, 1.378); P=0.385], UKB [OR=1.003; 95% CI=(0.827, 1.217); P=0.098]} and RVO. Using two-sample MR analysis, our study suggested that dyslipidemia was a risk factor for RVO. Furthermore, our results indicated that a low HDL-C level may be an independent risk factor for RVO, suggesting that controlling HDL-C level may be effective in RVO development.

BackgroundThe causal effect of obesity on diabetic retinopathy (DR) remains controversial. The aim of this study was to assess the causal association of generalized obesity evaluated by body mass index (BMI) and abdominal obesity evaluated by waist or hip circumference with DR, background DR, and proliferative DR using a two-sample Mendelian randomization (MR) analysis.MethodsGenetic variants associated with obesity at the genome-wide significance (P<5×10−8) level were derived using GWAS summary statistics from the UK Biobank (UKB) with a sample size of 461 460 individuals for BMI, 462 166 individuals for waist circumference, and 462 117 individuals for hip circumference. We obtained genetic predictors of DR (14 584 cases and 202 082 controls), background DR (2026 cases and 204 208 controls), and proliferative DR (8681 cases and 204 208 controls) from FinnGen. Univariable and multivariable Mendelian randomization analyses were conducted. Inverse variance weighted (IVW) was the main method used to analyze causality, accompanied by several sensitivity MR analyses.ResultsGenetically predicted increased BMI [OR=1.239; 95% CI=(1.134, 1.353);P=1.94×10-06], waist circumference [OR=1.402; 95% CI=(1.242, 1.584); P=5.12×10-08], and hip circumference [OR=1.107; 95% CI=(1.003, 1.221); P=0.042] were associated with increased risk of DR. BMI [OR=1.625; 95% CI=(1.285, 2.057); P=5.24×10-05], waist circumference [OR=2.085; 95% CI=(1.54, 2.823); P=2.01×10-06], and hip circumference [OR=1.394; 95% CI=(1.085, 1.791); P=0.009] were correlated with the risk of background DR. MR analysis also supported a causal association between BMI [OR=1.401; 95% CI=(1.247, 1.575); P=1.46×10-08], waist circumference [OR=1.696; 95% CI=(1.455, 1.977); P=1.47×10-11], and hip circumference [OR=1.221; 95% CI=(1.076, 1.385); P=0.002] and proliferative DR. The association of obesity with DR continued to be significant after adjustment for type 2 diabetes.ConclusionThis study using two-sample MR analysis indicated that generalized obesity and abdominal obesity might increase the risk of any DR. These results suggested that controlling obesity may be effective in DR development.

BackgroundCoronavirus disease 2019 (COVID-19) has brought great challenges to the global public health system and huge economic burdens to society, the causal effect of COVID-19 and intraocular pressure was blank.ObjectiveThis study aimed to explore the causal association between coronavirus disease (COVID-19) susceptibility, severity and criticality and intraocular pressure (IOP) by bidirectional Mendelian randomization (MR) analysis.Materials and methodsGenetic associations with COVID-19 susceptibility, severity and criticality were obtained from the COVID-19 Host Genetics Initiative. Genetic associations with IOP were obtained from GWAS summary data. The standard inverse variance weighted (IVW) method was used in the primary assessment of this causality. Other methods were also implemented in supplementary analyses. Finally, sensitivity analysis was performed to evaluate the reliability and stability of the results.ResultsThe results showed that COVID-19 susceptibility had null effect on IOP (β = 0.131; Se = 0.211; P = 0.533) as assessed by the IVW method. Moreover, the results revealed that COVID-19 severity, specifically, hospitalization due to COVID-19, had a positive effect on IOP with nominal significance (β = 0.228; Se = 0.116; P = 0.049). However, there were null effect of COVID-19 criticality on IOP (β = 0.078; Se = 0.065; P = 0.227). Sensitivity analysis showed that all the results were reliable and stable. The reverse MR analysis revealed that there was null effect of IOP on COVID-19.ConclusionsWe demonstrated that hospitalization due to COVID-19 might increase IOP; therefore, greater attention should be given to monitoring IOP in inpatients with COVID-19.