Abstract
Purpose :
Smoking is a well-known risk factor in age related macular degeneration (AMD) and age-related cataracts. Observational studies examining the relationship between smoking and glaucoma have been contradictory and there is no accepted causal association. Glaucoma is a leading cause of blindness, for which elevated intraocular pressure (IOP) is the only established modifiable risk factor. Mendelian randomisation (MR) uses the principle of Mendel's 2nd law of inheritance whereby inheritance of one trait is mutually exclusive of another. MR can assess whether a genetic propensity for smoking is associated with eye diseases, including glaucoma. Other traits are randomly distributed at meiosis thus minimising confounding.
Methods :
We completed an MR investigation using published data. Participants included a total of 361,194 individuals from UK Biobank. We considered single nucleotide variants (SNPs) which are associated with smoking behaviour at genome-wide significance. We tested their association with AMD, glaucoma and cataracts.
Results :
Our evidence suggests that smoking increases the risk of glaucoma (p<0.001) and cataracts (p<0.001). There was no association between smoking and AMD.
Conclusions :
This is the first MR study to investigate an association between smoking and eye disease. The positive association with glaucoma adds weight towards a causal effect, which may be vascular in origin. The lack of association of smoking with AMD may be a type 2 error: UK Biobank AMD data is self-reported and from a relatively young cohort, both factors which reduce case numbers and therefore power. Further work includes replicating the MR study in other datasets, including other ethnicities, and examining the impact of other modifiable risk factors in eye disease. Our study supports the use of MR and the UK Biobank as valuable tools in understanding risk factors in complex disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.