Association between myopia and diabetic retinopathy: A two-sample mendelian randomization study

Abstract

ObjectiveThe association between myopia and diabetic retinopathy (DR) is unclear, with inconsistent results reported, and whether the association represents causality remains unknown. This study aimed to investigate the causal associations of genetically determined myopia with DR, and further explore specific mechanisms. MethodsWe conducted two-sample mendelian randomization (MR) analyses of any myopia and high myopia on six DR phenotypes, including any DR, background DR, severe background DR, proliferative DR (PDR), diabetic maculopathy and unspecific DR in the primary study. Mechanism exploration of spherical equivalent refraction (SER), corneal curvature (CC) and axial length (AL) on any DR was carried out subsequently. Single-nucleotide polymorphisms (SNPs), used as genetic instruments, were derived from UK Biobank, Genetic Epidemiology Research on Adult Health and Aging cohort and FinnGen. The inverse variance weighted (IVW) method was mainly used to assess the causality, and was complemented with sensitivity analyses and causality direction analyses. ResultsUsing SNPs that have excluded possible confounders, we discovered suggestive and positive causal associations of any myopia with any DR (IVW: odds ratio [OR] = 1.133, 95% confidence interval [95%CI]: 1.070–1.201, P = 1.91×10−5) and PDR (IVW: OR = 1.182, 95%CI: 1.088–1.285, P = 8.31×10−5). Similar but more significant associations were found of high myopia with any DR and PDR (IVW: OR = 1.107, 95%CI: 1.051–1.166, P = 1.39×10−4; OR = 1.163, 95%CI: 1.088–1.244, P = 8.76×10−6, respectively). Further mechanism analyses found only AL, rather than SER or CC, was strongly and significantly associated with any DR. These associations were robust in sensitivity analyses and causality direction analyses. ConclusionsWe found significant and positive causal associations of any myopia and high myopia with the risk of DR and PDR, which might be related with AL, indicating the significance of myopia control for preventing DR development and progression.