Phenome-wide Mendelian randomisation analysis identifies causal factors for age-related macular degeneration.

Thomas H. Julian, Johnathan Cooper-Knock, Stuart Macgregor, Hui Guo, Tariq Aslam, Eleanor Sanderson, Graeme Black, Panos Sergouniotis

Research output: Contribution to journalArticlepeer-review


Age-related macular degeneration (AMD) is the leading cause of blindness in the industrialised world and is projected to affect 288 million people worldwide by 2040. Aiming to identify causal factors for this common disorder, we designed and applied a phenome-wide Mendelian randomisation (MR) approach to identify therapeutic targets and avenues for future research.

We evaluated the effect of 4,591 exposure traits on early AMD using univariable MR. Statistically significant results were explored further using validation in an advanced AMD cohort, MR Bayesian model averaging (MR BMA) and multivariable MR.

44 traits were found to be putatively causal for early AMD in univariable analysis. MR BMA of lipid traits suggested a causal role for serum sphingomyelin (marginal inclusion probability=0.76, model averaged causal effect=0.29). Univariable MR analysis supported roles for complement and immune cell traits. Serum proteins were found to have significant relationships with AMD including S100-A5 (Odds ratio (OR)= 1.07, p = 6.80E-06), cathepsin F (OR=1.10, p = 7.16E-05) and serine palmitoyltransferase 2 (OR= 0.86, p value=1.00E-03).

The results of this study support several putative causal factors in AMD and highlight avenues for future clinical research.
Original languageEnglish
Publication statusAccepted/In press - 18 Dec 2022


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