Exploring the Associations of Obesity and Glycemic Traits with Retinal Vein Occlusion: A Univariate and Multivariable Mendelian Randomization Study

To explore the genetic links between obesity, glycemic traits and retinal vein occlusion (RVO). Summary-level statistics for obesity and glycemic traits were extracted from publicly available genome-wide association studies (GWAS) of European participants in the IEU Open GWAS database. Genetic associations with clinically diagnosed RVO were obtained from the FinnGenresearch project (372 cases and 182,573 controls). Two-sample Mendelian randomization (MR) and multivariate MR (MVMR) analysis were performed to determine the total effect and direct effect, respectively. After adjustment for the false discovery rate (FDR), the primary inverse-variance-weighted (IVW) methods indicated that the odds ratios of RVO increased with per 1-standard deviation increased in body mass index (BMI) (OR = 1.94, 95% CI: 1.23–3.08,<i>p</i>-FDR = 0.025), waist circumference (OR = 2.4, 95% CI: 1.36–4.24, <i>p</i>-FDR = 0.019), fasting glucose (OR = 5.01, 95% CI: 2–12.55, <i>p</i>-FDR = 0.0067) and two-hour glucose (OR = 3.17, 95% CI: 1.63–6.18,<i>p</i>-FDR = 0.0067). Higher whole-body fat-free mass (OR = 0.45, 95% CI: 0.26–0.8,<i>p</i>-FDR = 0.025) is a potential protective factor for RVO. In addition, the results of MVMR showed that BMI, whole-body fat-free mass, fasting glucose and two-hour glucose were independent factors that had a direct impact on the onset of RVO. Our comprehensive MR analysis suggested significant genetic associations between BMI, whole-body fat-free mass, fasting glucose, two-hour glucose and RVO. This study highlighted the importance of weight, blood glucose management and physical activity for primary prevention and control of RVO.