Increased alcohol intake causal risk factor for Geographic atrophy in eye: JAMA

Mendelian randomization (MR) is a technique that has been used to assess potential causal associations across a wide range of diseases. MR is based on the principle that if a genetic variant causes a change in an exposure (eg, smoking or alcohol intake), and if this exposure is causal for a disease (eg, advanced AMD), then the genetic variant should also be associated with risk of the disease. Valerie Kuan and team used MR to assess the potential causal role of other exposures that are amenable to intervention (ie, smoking, alcohol intake, bodymass index [BMI], blood pressure, and glycemic traits) on the risk of advanced AMD and its subtypes, GA and nAMD, using publicly available data.

This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P < 5 × 10−8) were obtained from published genome-wide association studies. Summary-level statistics for these instruments were obtained for advanced AMD from the International AMD Genomics Consortium 2016 data set, which consisted of 16,144 individuals with AMD and 17,832 control individuals. Data were analyzed from July 2020 to September 2021. Exposure included smoking initiation, smoking cessation, lifetime smoking, age at smoking initiation, alcoholic drinks per week, body mass index, systolic and diastolic blood pressure, type 2 diabetes, glycated hemoglobin, fasting glucose, and fasting insulin. Outcomes included Advanced AMD and its subtypes, geographic atrophy (GA), and neovascular AMD.

• A 1-SD increase in logodds of genetically predicted smoking initiation was associated with higher risk of advanced AMD (P < .001), while a 1-SD increase in logodds of genetically predicted smoking cessation (former vs current smoking) was associated with lower risk of advanced AMD (P = .003).

• Genetically predicted increased lifetime smoking was associated with increased risk of advanced AMD (OR per 1-SD increase in lifetime smoking behavior,P = .004).

• Genetically predicted alcohol consumption was associated with higher risk of GA (OR per 1-SD increase of log-transformed alcoholic drinks per week, P = .001).

• There was insufficient evidence to suggest that genetically predicted blood pressure, body mass index, and glycemic traits were associated with advanced AMD.

Authors found genetic evidence supporting a potential causal association between smoking initiation and advanced AMD risk consistent with previous observational studies. This association was stronger for nAMD than for GA. Similar results were found for lifetime smoking behavior. Additionally, smoking cessation was associated with a decreased risk of advanced AMD, specifically nAMD, compared with persistent smoking. Study also found suggestive evidence for a possible causal association between increased alcohol consumption and risk of advanced AMD that was likely driven by a strong association with GA. There was insufficient evidence to suggest a potential causal association with the other exposures, namely BMI, blood pressure, or glycemic risk factors, on advanced AMD risk.

This study provides genetic evidence that smoking initiation and lifetime smoking behavior are potential causal risk factors for advanced AMD, and that stopping smoking may be protective against the risk of advanced AMD. The detrimental effects of smoking on multiple conditions, such as cardiovascular disease, cancers, and chronic obstructive pulmonary disease, are well known. Public health campaigns should disseminate information that smoking can also lead to blindness as an additional deterrent against smoking.

Study also found genetic evidence that increased alcohol consumption has a potential causal association with GA risk. Here again, public health messages and clinical advice regarding the harms of excessive alcohol intake should include the risk of blindness, especially given that there are currently no effective treatments for GA. Given the deterioration in quality of life and the cost to health and social care systems of managing advanced AMD, increased funding should be allocated to smoking cessation and alcohol reduction programs to minimize the health burden of advanced AMD

Study found genetic evidence that increased alcohol consumption has a potential causal association with risk of GA. Study also present genetic evidence that smoking initiation and lifetime smoking behavior may be casually associated with risk of advanced AMD, while smoking cessation results in a lower risk of advanced AMD than persistent smoking. These associations were stronger for nAMD than for GA. To reduce the prevalence of advanced AMD in aging populations, public health campaigns and programs to support smoking abstention, smoking cessation, and reduced alcohol intake should incorporate the evidence that these activities can lead to blindness. The finding that smoking and alcohol have differential effects on nAMD and GA may prompt future studies examining the different pathologies of these 2 forms of advanced AMD.

Source: doi:10.1001/jamaophthalmol.2021.4601