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Age-related macular degeneration is a risk factor for COVID-19 infection and severe disease

Age-related macular degeneration is a risk factor for COVID-19 infection and severe disease

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Summary: More severe outcomes of COVID-19 associated with age-related macular degeneration likely arise from genetic predisposition in addition to higher blood serum Pdgf levels.

source: Boston University

Recent evidence has emerged to suggest that age-related macular degeneration (AMD) is a clinical risk factor for increased risk of infection and mortality. AMD has been reported to confer a higher risk of severe complications of SARS-CoV-2 infection, including respiratory failure and death (25 percent), a risk that is higher than type 2 diabetes (21 percent) and obesity (13 percent).

With these observations in mind, researchers at Boston University Chobanian & Avedisian School of Medicine hypothesized that AMD and COVID-19 share common genetic risk factors and designed and executed a study that identified a new association of the two diseases with variants in PDGFB gen. This gene codes for platelet-derived growth factor (Pdgf), which plays a role in the formation of new blood vessels and is involved in the abnormal changes in blood vessels that occur in AMD.

They also found that more severe outcomes from COVID-19 were associated with AMD, possibly resulting from a genetic predisposition to dysfunction involving complement proteins, as well as a higher level of Pdgf in the blood serum.

“Our findings add to the body of evidence for the increased risk of infection and mortality from COVID-19 among patients with AMD. Our analysis lends credence to previously reported clinical studies that found that people with AMD have a higher risk of COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” explained co-author Lindsey A. Farrer, Ph.D., Head of Biomedical Genetics.

The BU research team conducted a genome-wide search for variants that are jointly associated with AMD and each of the three outcomes of COVID-19 (infection rate, critical illness, and hospitalization) using large genetic data sets that contain tens of thousands of individuals . These datasets were previously collected and examined separately for genetic factors contributing to AMD risk and for each of the COVID-19 disease outcomes.

The researchers then analyzed publicly available data from patients with AMD or COVID-19 and control groups to assess the association of the variants in PDGFB with gene activity.

Finally, they used an analytical technique that allowed them to examine causal relationships between PDGFB gene variants, Pdgfb blood concentration, AMD and COVID-19 outcomes.

According to the researchers, these findings suggest that lowering PDGFB gene activity and serum PDGF concentration may reduce the severity of COVID-19, especially among the elderly.

This gene codes for platelet-derived growth factor (Pdgf), which plays a role in the formation of new blood vessels and is involved in the abnormal changes in blood vessels that occur in AMD. Image is in the public domain

“Therapeutic strategies combining anti-VEGF therapy (a current treatment for AMD that restricts the growth of blood vessels in the eye, which can damage vision) with antagonists (drugs that bind to the receptors) to block PDGF signaling are even considered to be more effective than single VEGF treatment and are currently being studied in clinical trials,” added co-author Manju L. Subramanian, MD, associate professor of ophthalmology.

The researchers believe that this discovery of shared genetic risk factors will require a larger sample size for critical illnesses and hospitalizations to better understand the shared pathology and risk factors that contribute to worse clinical outcomes in both disease states .

Financing: This work was supported by National Institutes of Health grants RF1 AG057519, R01 AG069453, R01 AG048927, U19 AG068753, and U01 AG062602.

About this AMD and COVID-19 research news

Author: Gina DiGravio
source: Boston University
Contact: Gina DiGravio – Boston University
Image: Image is in the public domain

See also

Age-related macular degeneration is a risk factor for COVID-19 infection and severe disease

Original research: Free access.
Genome-wide pleiotropy study identifies association of PDGFB with age-related macular degeneration and outcomes of COVID-19 infection” by Lindsay A. Farrer et al. Journal of Clinical Medicine


Summary

Genome-wide pleiotropy study identifies association of PDGFB with age-related macular degeneration and outcomes of COVID-19 infection

Age-related macular degeneration (AMD) has been implicated as a risk factor for severe outcomes from COVID-19.

We assessed the genetic architecture shared between AMD and COVID-19 (critical illness, hospitalization, and infections) using genetic correlation and pleiotropy (i.e., cross-phenotype meta-analysis) analyzes of AMD (n = 33,976) and COVID-19 (n ≥ 1,388,342) and subsequent analyzes including expression quantitative trait locus (eQTL), differential gene expression and Mendelian randomization (MR). We observed a significant genetic correlation between AMD and COVID-19 infection (rZ = 0.10, p = 0.02) and identified novel genome-wide significant associations near PDGFB (best SNP: rs130651; p = 2.4 × 10-8) in the pleiotropic analysis of the two diseases.

The disease risk allele of rs130651 was significantly associated with increased gene expression levels of PDGFB in multiple tissues (best eQTL p = 1.8 × 10-11 in whole blood) and immune cells (top eQTL p = 7.1 × 10-20 in T cells). PDGFB expression was observed to be higher in AMD cases than AMD controls {fold change (FC) = 1.02; p = 0.067}, as well as in the peak stage of COVID-19 symptoms (11–20 days after the onset of symptoms) compared to the early/progressive stage (0–10 days) among patients with COVID-19 aged over 40 years ( FC = 2.17; p = 0.03) and age 50 (FC = 2.15; p = 0.04). Our MR analysis found that responsibility for AMD risk stems from dysfunction of the complement system {OR (95% CI); hospitalization = 1.02 (1.01–1.03), infection = 1.02 (1.01–1.03), and elevated levels of serum cytokine PDGF-BB {β (95% CI); critical illness = 0.07 (0.02–0.11)} were significantly associated with COVID-19 outcomes.

Our study showed that AMD liability is associated with an increased risk of COVID-19, and PDGFB may be responsible for the severe outcomes of COVID-19 among AMD patients.


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