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Age-related macular degeneration is a risk factor for COVID-19 infection and serious illness

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

Source: boston university

Recent evidence suggests 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 greater risk of serious complications from SARS-CoV-2 infection, including respiratory failure and death (25%), a greater risk than type 2 diabetes (21%) and obesity (13%).

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

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

“Our findings add to the body of evidence for an increased risk of COVID-19 infection and mortality among patients with AMD. Our analysis lends credence to previously reported clinical studies that found that those with AMD have an increased risk of COVID-19 infection and severe illness, and that this increased risk may have a genetic basis,” explained co-author Lindsay A. Farrer , PhD, head of biomedical genetics.

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

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

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

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

It shows an older man's eye
This gene encodes a platelet-derived growth factor (Pdgf) that plays a role in the formation of new blood vessels and is involved in the abnormal blood vessel changes that occur in AMD. The image is in the public domain

“Therapeutic strategies that combine anti-VEGF therapy (a current treatment for AMD that limits the growth of blood vessels in the eye that can impair vision) with antagonists (drugs that bind to receptors) to block PDGF signaling have been considered even more effective than VEGF alone and are currently under investigation in clinical trials,” added co-corresponding 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 illness and hospitalizations to better understand shared pathology and risk factors that contribute to worsening 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 Di Gravio
Source: boston university
Contact: Gina DiGravio – Boston University
Image: The image is in the public domain

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Original search: Free access.
“Genomewide 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 identified as a risk factor for severe consequences of COVID-19.

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

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

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

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