Genetically determined plasma lipid levels and risk of diabetic retinopathy: A mendelian randomization study

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization (MR) approach. We pooled genome-wide association studies summary statistics from 18 studies for 2 DR phenotypes: any DR (N = 2,969 case; 4,096 controls) and severe DR, (N = 1,277 cases; 3,980 controls). Previously identified lipid-associated single nucleotide polymorphisms (SNPs) served as instrumental variables. Meta-analysis to combine the MR estimates from different cohorts was conducted. There was no statistically significant change in odds ratios (OR) of having any DR or severe DR for any of lipid fractions in the primary analysis which used SNPs that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect OR less than 1.23 per standard deviation (SD) in genetically-induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist.