Causal factors in primary open angle glaucoma: a phenome-wide Mendelian randomisation study.

Primary open angle glaucoma (POAG) is a chronic, adult-onset optic neuropathy associated with characteristic optic disc and/or visual field changes. With a view to identifying modifiable risk factors for this debilitating condition, we performed a phenome-wide univariable Mendelian randomisation (MR) study and analysed the relationship between 9,661 traits and POAG. Data were analysed using the weighted median method, weighted mode based estimation, the Mendelian randomisation (MR) Egger method and the inverse variance weighted approach. Our analysis identified 11 traits related to POAG risk including: serum levels of the angiopoietin-1 receptor (OR [odds ratio] = 1.11, IVW [inverse variance weighted] p= 2.34E-06) and the cadherin 5 protein (OR= 1.06, IVW p= 1.31E-06); intraocular pressure (OR=2.46 - 3.79, MRE IVW p=8.94E-44 - 3.00E-27); diabetes (beta=1.64, IVW p = 9.68E-04); and waist circumference (OR = 0.79, IVW p=1.66E-05). Future research focussing on the effects of diabetes, waist circumference, serum cadherin 5 and serum angiopoietin-1 receptor on POAG development and progression is expected to provide key insights that might inform the provision of lifestyle modification advice and/or the development of novel therapies.