Ethnic Heterogeneity in the Causal Effect of Obesity on Diabetic Retinopathy: A Multi-Population Mendelian Randomization Study

Background: Diabetic retinopathy is one of the microvascular complications and a significant cause of blindness that is mostly associated with diabetes.Obesity using BMI as a measure is also associated with type 2 diabetes; however, its direct pathway to DR is not obvious or may differ among ethnic groups.Objective: To conduct a two-sample MR analysis to quantify the causal effect of obesity on DR in different populations, and to examine ethnic differences in this association.Methods: Specific genetic loci related to BMI were identified from the genome-wide association studies with three independent populations: European (UK Biobank), East Asian (Biobank Japan, GenomeAsia100K) and South Asian (INDIAB Extension).The MR analyses were undertaken with IVW, MR-Egger regression, and the weighted median approaches.Heterotopic MR-Egger intercepts and F-statistics were used to assess horizontal pleiotropy and the strength of instruments.Stratified and sensitivity analyses were performed to make the study less vulnerable.Results: In the European cohort, note a robust causal risk association between BMI and DR was established (IVW OR = 1.18; 95% CI: 1.09 to 1.28; p = 0.0003).It however emerged that this association was not noticeable in the East Asia or South Asian groups of people.MR-Egger