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Zijun Yu, Xiaoran Chai, Sahil Thakur, Chiea Chuen Khor, Xueling Sim, Tin Aung, Tien Y Wong, Eranga Nishanthie Vithana, Qiao Fan, Ching-Yu Cheng; Serum lipid Levels and Glaucoma: A Mendelian Randomisation Analysis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1962.
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Serum lipid levels have been implicated in the development of primary open angle glaucoma (POAG). In particular, hypertriglyceridemia and low-density lipoprotein cholesterol (LDL-C) were implicated in the pathogenesis of POAG. However, observational studies might have yielded ambiguous relationships regarding the association of lipid levels and glaucoma due to unmeasured or unknown confounders. We aim to use Mendelian Randomisation (MR) analysis to determine the effect of lipid levels on POAG.
We investigated the association between subcategories of lipid levels and POAG in East Asian populations, comprising of 5013 POAG cases and 21186 controls, using Mendelian randomisation analysis. We identified a total of 156 SNPs associated with triglyceride, LDL-C, and high-density lipoprotein cholesterol (HDL-C) from published genome-wide association studies. These SNPs were used as instrumental variables (IV) for the MR analysis, which capitalises on the randomisation of genetic variants inherited independent of potential confounding factors of lifestyle and environment. The 156 SNPs explained an estimated 2.22%, 1.95% and 3.27% of the variability of triglyceride, LDL-C, and HDL-C respectively.
We performed 2 models of analysis. Model 1 is a fixed-effect meta-analysis weighted by inverse variance. Model 2 is a multivariable MR-Egger regression analysis, accounting for pleiotropic effects from other lipid subcategories. Using Model 1 (Table), MR analysis showed that triglyceride level was not significantly associated with POAG (odds ratio = 0.96 per one standard deviation (SD) increase in triglyceride levels, 95% confidence interval: 0.86-1.11; p value = 0.76) in East Asians. Similarly, there was no significant association between LDL-C levels and POAG (OR=0.92, P = 0.23), or between HDL-C, and POAG (OR=0.96, P =0.51). The results of Model 2 were essentially similar.
Using the Mendelian randomisation analysis, our study shows no evidence of a causal association between the lipid fractions and POAG in East Asian populations. Further analysis using MR-Egger multivariable regression accounting for pleiotropic effects of other potentially associated traits such as body mass index and hypertension, can be conducted to identify the effect of individual lipid fraction on POAG.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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