Dataset Information

Rare and Common Genetic Variants, Smoking, and Body Mass Index: Progression and Earlier Age of Developing Advanced Age-Related Macular Degeneration.

ABSTRACT:

Purpose

To determine behavioral and genetic factors associated with incidence and age of progression to advanced age-related macular degeneration (AMD), geographic atrophy (GA), and neovascular disease (NV), and to quantify these effects.

Methods

Longitudinal analyses were conducted among 5421 eyes with nonadvanced AMD at baseline in 2976 participants in the Age-Related Eye Disease Study (mean age of 68.8 (±5.0), 56.1% female). Progression was confirmed based on two consecutive visits on the AMD severity scale. Separate analyses for progression and age of progression were performed. All analyses adjusted for correlation between eyes, demographic and behavioral covariates, baseline severity scale, and genetic variants.

Results

A higher genetic risk score (GRS) including eight genetic variants was associated with a higher rate of progression to advanced AMD within each baseline severity scale, especially for the highest risk intermediate level AMD category, and smoking further increased this risk. When assessing age when progression to advanced disease occurred, smoking reduced age of onset by 3.9 years (P < 0.001), and higher body mass index (BMI) led to earlier onset by 1.7 years (P = 0.003), with similar results for GA and NV. Genetic variants associated with earlier age of progression were CFH R1201C (4.3 years), C3 K155Q (2.15 years), and ARMS2/HTRA1 (0.8 years per allele).

Conclusions

Rare variants in the complement pathway and a common risk allele in ARMS2/HTRA1, smoking, and higher BMI can lead to as much as 11.5 additional years of disease and treatment burden. Closer adherence to healthy lifestyles could reduce years of visual impairment.

SUBMITTER: Seddon JM

PROVIDER: S-EPMC7774056 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Rare and Common Genetic Variants, Smoking, and Body Mass Index: Progression and Earlier Age of Developing Advanced Age-Related Macular Degeneration.

Seddon Johanna M JM Widjajahakim Rafael R Rosner Bernard B

Investigative ophthalmology & visual science 20201201 14

<h4>Purpose</h4>To determine behavioral and genetic factors associated with incidence and age of progression to advanced age-related macular degeneration (AMD), geographic atrophy (GA), and neovascular disease (NV), and to quantify these effects.<h4>Methods</h4>Longitudinal analyses were conducted among 5421 eyes with nonadvanced AMD at baseline in 2976 participants in the Age-Related Eye Disease Study (mean age of 68.8 (±5.0), 56.1% female). Progression was confirmed based on two consecutive vi ...[more]

PMID: 33369641

Similar Datasets

Project description:ImportanceAdvanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD.ObjectiveTo assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD.Design, setting, participantsThis 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.ExposuresSmoking 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.Main outcomes and measuresAdvanced AMD and its subtypes, geographic atrophy (GA), and neovascular AMD.ResultsA 1-SD increase in logodds of genetically predicted smoking initiation was associated with higher risk of advanced AMD (odds ratio [OR], 1.26; 95% CI, 1.13-1.40; 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 (OR, 0.66; 95% CI, 0.50-0.87; P = .003). Genetically predicted increased lifetime smoking was associated with increased risk of advanced AMD (OR per 1-SD increase in lifetime smoking behavior, 1.32; 95% CI, 1.09-1.59; 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, 2.70; 95% CI, 1.48-4.94; P = .001). There was insufficient evidence to suggest that genetically predicted blood pressure, body mass index, and glycemic traits were associated with advanced AMD.Conclusions and relevanceThis study provides genetic evidence that increased alcohol intake may be a causal risk factor for GA. As there are currently no known treatments for GA, this finding has important public health implications. These results also support previous observational studies associating smoking behavior with risk of advanced AMD, thus reinforcing existing public health messages regarding the risk of blindness associated with smoking.

Dataset Information

Rare and Common Genetic Variants, Smoking, and Body Mass Index: Progression and Earlier Age of Developing Advanced Age-Related Macular Degeneration.

Purpose

Methods

Results

Conclusions

Publications

Rare and Common Genetic Variants, Smoking, and Body Mass Index: Progression and Earlier Age of Developing Advanced Age-Related Macular Degeneration.

Similar Datasets

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