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

Background: Age-related macular degeneration (AMD) is a leading cause of blindness in the industrialised world and is projected to affect >280 million people worldwide by 2040. Aiming to identify causal factors and potential therapeutic targets for this common condition, we designed and undertook a phenome-wide Mendelian randomisation (MR) study. Methods: We evaluated the effect of 4591 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. Results: Overall, 44 traits were found to be putatively causal for early AMD in univariable analysis. Serum proteins that were found to have significant relationships with AMD included S100-A5 (odds ratio [OR] = 1.07, p-value = 6.80E−06), cathepsin F (OR = 1.10, p-value = 7.16E−05), and serine palmitoyltransferase 2 (OR = 0.86, p-value = 1.00E−03). Univariable MR analysis also supported roles for complement and immune cell traits. Although numerous lipid traits were found to be significantly related to AMD, MR-BMA suggested a driving causal role for serum sphingomyelin (marginal inclusion probability [MIP] = 0.76; model-averaged causal estimate [MACE] = 0.29). Conclusions: The results of this MR study support several putative causal factors for AMD and highlight avenues for future translational research

Decisions, disagreement and responsibility: towards an agonistic green citizenship

In recent explications of green citizenship, citizenship responsibilities are emphasised over citizenship rights. Too often it is assumed that deciding the content of these citizenship responsibilities and acting collectively in accordance with them is a straightforward matter of rational consensus. Using Mouffe's account of the political, this article argues that a rational and fully inclusive consensus is impossible. The inevitable conflict of the political realm, however, should not be seen as an obstacle to responsible collective action but rather as integral to the political decisions underpinning collective action. The article outlines a model of ‘agonistic green citizenship’ in which responsibility is understood in terms of acknowledging the irreducible disagreement arising from differently embodied citizens. The environment here is not simply an object of disagreement but contributes to the different perspectives that underpin that disagreement