Is Genetic Risk for Sleep Apnoea Causally Linked With Glaucoma Susceptibility?

Abstract

Background: Observational studies have suggested that individuals with pre-existing sleep apnoea (SA) have up to double the risk of developing glaucoma than individuals without SA. However, it is unclear if these associations are due to confounding or reverse causation. Disentangling causality from confounding is essential to further our understanding of both diseases. Mendelian randomisation (MR) techniques, which use genetic variants associated with a risk factor (e.g. SA) as instrumental variables (IVs), can be used to infer causality. MR methods can be less susceptible to confounders or reverse causation than observational studies. Methods: In this study, 34 IVs for SA were derived from a genome-wide association study (GWAS) of 25 008 SA cases, 313 372 controls. Two Sample MR analyses were performed to evaluate the relationship between genetically predicted SA and glaucoma susceptibility using summary data from a glaucoma GWAS meta-analysis (20 582 cases, 119 318 controls). We derived odds ratios (OR) for glaucoma arising from a doubling in the genetic odds of having SA. Finding: Using 34 SA SNPs as IVs, we found no strong evidence for an association between SA susceptibility and glaucoma (OR = 0.95, 95% confidence intervals = 0.77 - 1.13) based on the inverse variance weighted (IVW) MR estimator. Interpretation: We found little genetic evidence supporting a causal association between SA and glaucoma. Our results refute the possibility of a large effect (glaucoma OR > 1.5 per doubling of odds on SA) between SA and glaucoma. Funding Information: S.M. and D.A.M are supported by the Australian National Health and Medical Research Council (NHMRC) Fellowships. X.H. is supported by the University of Queensland Research Training Scholarship and QIMR Berghofer Medical Research Institute PhD Top Up Scholarship. We acknowledge funding from NHMRC grants 1123248, 1116360, 1150144, 1023911. A.I.C. is supported by a UQ Research Training Scholarship from The University of Queensland (UQ). M.E.R. acknowledges support from the NHMRC and Australian Research Council (ARC) through a Research Fellowship (GNT1102821). Declaration of Interests: There are no competing interest to disclose. Ethics Approval Statement: Both sources of GWAS summary statistics included here acquired appropriate ethical approval. No ethical approval was required for this study.