Effects of smoking, alcohol, blood pressure, body mass index and glycaemic risk factors on advanced age-related macular degeneration: a mendelian randomisation study

Abstract

Purpose : To assess whether smoking, alcohol consumption, body mass index (BMI), blood pressure (BP) and glycaemic traits have a causal role in the risk of advanced age-related macular degeneration (AMD).

Methods : We used two-sample inverse-variance weighted, MR-Egger and weighted median mendelian randomisation methods to investigate the association between modifiable risk factors (smoking, alcohol consumption, BMI, BP and glycaemic traits) and the risk of advanced AMD (neovascular AMD or geographic atrophy). Summary level genetic association data for advanced AMD (n=16,144) were obtained from the International AMD Genomics Consortium (IAMDGC) genome-wide association study (GWAS). Genetic instruments composed of single nucleotide polymorphisms associated with modifiable risk factors at genome-wide significance (P < 5×10⁻⁸) were obtained from published GWASs.

Results : Genetically predicted lifetime smoking was associated with increased advanced AMD risk (odds ratio (OR) per unit increase of the lifetime smoking index 1.49; 95% CI 1.13-1.95; P=0.004). Specifically, a one-standard deviation (SD) increase in log odds of ever smoking was associated with higher risk (OR 1.26; 95% CI 1.13-1.40; P<0.001), while a one-SD increase in log odds of smoking cessation (former versus current smoking) was associated with lower risk (OR 0.66; 95% CI 0.50-0.87; P=0.003). A one-SD increase of log-transformed alcoholic drinks per week was suggestive of an association with higher risk of advanced AMD (OR 1.57; 95% CI 1.03-2.40; P=0.04). There was insufficient evidence to suggest associations with genetically predicted BP, BMI and glycaemic traits (figure).

Conclusions : This study provides genetic evidence that ever smoking is causal for advanced AMD risk, while smoking cessation is protective. The evidence also suggests that increased alcohol intake is a causal risk factor. Public health messages regarding the adverse consequences of smoking and excessive alcohol consumption should include warnings about the risk of blindness.

This is a 2021 ARVO Annual Meeting abstract.

 

Association of modifiable risk factors with advanced age-related macular degeneration risk using inverse variance weighted mendelian randomisation.