Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors

Pennington, Karen L.; DeAngelis, Margaret M.

doi:10.1186/s40662-016-0063-5

Cited by 406 publications

(327 citation statements)

References 216 publications

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“…In addition, there was a highly significant risk effect (OR = 1.36) of HDL-c on age-related macular degeneration (AMD) in the case-control data. The associations between lipids and AMD are controversial and results from different observational studies are inconsistent 42 . Our results support the observations that increased HDL-c is associated with increased risk of AMD [42][43][44] .…”

Section: "Good" Vs "Bad" Cholesterolmentioning

confidence: 99%

Causal associations between risk factors and common diseases inferred from GWAS summary data

Zhu

Zheng

Zhang

et al. 2017

Preprint

147

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Health risk factors such as body mass index (BMI), serum cholesterol and blood pressure are associated with many common diseases. It often remains unclear whether the risk factors are cause or consequence of disease, or whether the associations are the result of confounding.Genetic methods are useful to infer causality because genetic variants are present from birth and therefore unlikely to be confounded with environmental factors. We develop and apply a method (GSMR) that performs a multi-SNP Mendelian Randomization analysis using summarylevel data from large genome-wide association studies (sample sizes of up to 405,072) to test the causal associations of BMI, waist-to-hip ratio, serum cholesterols, blood pressures, height and years of schooling (EduYears) with a range of common diseases. We identify a number of causal associations including a protective effect of LDL-cholesterol against type-2 diabetes (T2D) that might explain the side effects of statins on T2D, a protective effect of EduYears against Alzheimer's disease, and bidirectional associations with opposite effects (e.g. higher BMI increases the risk of T2D but the effect T2D of BMI is negative). HDL-cholesterol has a significant risk effect on age-related macular degeneration, and the effect size remains significant accounting for the other risk factors. Our study develops powerful tools to integrate summary data from large studies to infer causality, and provides important candidates to be prioritized for further studies in medical research and for drug discovery.

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Section: "Good" Vs "Bad" Cholesterolmentioning

confidence: 99%

Causal associations between risk factors and common diseases inferred from GWAS summary data

Zhu

Zheng

Zhang

et al. 2017

Preprint

147

View full text Add to dashboard Cite

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“…3 Despite the fact that significant efforts have been made to identify risk factors of AMD, currently, there are no recognized methods to prevent it. 4 For these reasons, there is an urgent need to develop effective interventions to prevent the progression of early AMD to late AMD. Except for smoking cessation and avoidance of cigarette smoke exposure, effective treatment options for early AMD…”

Section: Introductionmentioning

confidence: 99%

Identification of lncRNAs involved in biological regulation in early age-related macular degeneration

Zhu

Xing

et al. 2017

IJN

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Background Age-related macular degeneration (AMD) is one of the most common causes of adult blindness in developed countries. However, the role of long noncoding RNAs (lncRNAs) in the development and progression of early AMD is unclear. Methods We established the lncRNA profile of early AMD by reannotation of microarrays from the gene expression omnibus database. Quantitative real-time polymerase chain reaction was used to determine the expression of selected lncRNAs. Results The expression profiles of 9 cases of AMD and 7 controls were studied. A total of 266 differentially expressed genes (DEGs) were detected (94 upregulated and 172 downregulated). Among all the DEGs, 64 were lncRNAs. Advanced bioinformatics analyses demonstrated that differentially expressed lncRNAs could play significant roles in visual perception, sensory perception of light stimulus, and cognition. The pathway analyses showed that the two most significantly influenced Kyoto Encyclopedia of Genes and Genomes pathways were those of phototransduction and purine metabolism. By the analyses of the key lncRNAs, it was found that RP11-234O6.2 was downregulated in the aging retinal pigment epithelium (RPE) cellular model. Exogenous RP11-234O6.2 treatment led to increased cell viability and improved apoptosis but it did not affect the cell migration ability of aging RPE cells. Conclusion This study indicated that lncRNAs are differentially expressed in early AMD and may produce important regulative effects. An lncRNA, RP11-234O6.2, might be involved in the biological regulation of early AMD and have therapeutic potential.

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“…It is estimated that there are approximately 170 million people with AMD. This is projected to increase to approximately 196 million people by 2020 and 288 million people by 2040 . AMD is divided into early, intermediate and late stages with the disease progressing in the late stages to be either neovascular that is, wet AMD or dry geographic atrophy .…”

Section: Ocular Diseases Targeted By Aav Gene Therapy In Humansmentioning

confidence: 99%

“…This is projected to increase to approximately 196 million people by 2020 and 288 million people by 2040. 94,95 AMD is divided into early, intermediate and late stages with the disease progressing in the late stages to be either neovascular that is, wet AMD or dry geographic atrophy. 96 Early AMD is usually diagnosed by the presence of drusen, yellow fatty deposits under the retina, and is typically not associated with vision loss.…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

Gene therapy and the adeno‐associated virus in the treatment of genetic and acquired ophthalmic diseases in humans: Trials, future directions and safety considerations

Ramlogan‐Steel

Murali

Andrzejewski

et al. 2019

Clinical Exper Ophthalmology

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Voretigene neparvovec‐rzyl was recently approved for the treatment of Leber congenital amaurosis, and the use of gene therapy for eye disease is attracting even greater interest. The eye has immune privileged status, is easily accessible, requires a reduced dosage of therapy due to its size and is highly compartmentalized, significantly reducing systemic spread. Adeno‐associated virus (AAV), with its low pathogenicity, prolonged expression profile and ability to transduce multiple cell types, has become the leading gene therapy vector. Target diseases have moved beyond currently untreatable inherited dystrophies to common, partially treatable acquired conditions such as exudative age‐related macular degeneration and glaucoma, but use of the technology in these conditions imposes added obligations for caution in vector design. This review discusses the current status of AAV gene therapy trials in genetic and acquired ocular diseases, and explores new scientific developments, which could help ensure effective and safe use of the therapy in the future.

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Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors

Cited by 406 publications

References 216 publications

Causal associations between risk factors and common diseases inferred from GWAS summary data

Causal associations between risk factors and common diseases inferred from GWAS summary data

Identification of lncRNAs involved in biological regulation in early age-related macular degeneration

Gene therapy and the adeno‐associated virus in the treatment of genetic and acquired ophthalmic diseases in humans: Trials, future directions and safety considerations

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