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

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

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

Abstract: More severe outcomes of COVID-19 associated with age-related macular degeneration likely result from a genetic predisposition with higher serum Pdgf levels.

Source: Boston University

Recently, 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 carry a higher risk of severe complications of SARS-CoV-2 infection, including respiratory failure and death (25 percent), a risk that is greater than type 2 diabetes (21 percent) and obesity (13 percent).

Taking these observations into account, researchers from the Boston University Chobanian & Avedisian School of Medicine hypothesized that AMD and COVID-19 share common genetic risk factors and designed and conducted a study that identified a new association between the two diseases with variants in PDGFB gene. This gene encodes 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 of COVID-19 are associated with AMD that likely results from a genetic predisposition to dysfunction involving complement proteins, as well as higher serum levels of Pdgf.

“Our findings add to the body of evidence of an 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 are at increased risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” explained co-author Dr. Lindsay A. Farrer. , head of biomedical genetics.

The BU research team conducted a genome-wide search for variants jointly associated with AMD and each of the three outcomes of COVID-19 (infection rate, critical illness, and hospitalization) using large genetic datasets containing tens of thousands of individuals. These datasets were previously collected and studied 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 variants in PDGFB with gene activity.

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

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

Age-related macular degeneration is a risk factor for infection and serious diseases of COVID-19
This gene encodes 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. 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 damage vision) with antagonists (drugs that bind to receptors) to block PDGF signaling are thought to be even more effective than VEGF alone. treatment and are currently under investigation 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 illness and hospitalizations to better understand the 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 DiGravio
Source: Boston University
Contact: Gina DiGravio – Boston University
Picture: The image is in the public domain

See also

This shows a drawing of the brain

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


Abstract

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

Age-related macular degeneration (AMD) is considered a risk factor for serious consequences of COVID-19.

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

The disease risk allele of rs130651 was significantly associated with increased gene expression levels PDGFB in multiple tissues (best eQTL p = 1.8 × 10-11 in whole blood) and immune cells (best 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 in the peak stage of symptoms of COVID-19 (11-20 days after the onset of symptoms) compared to the early/progressive stage (0-10 days) among patients with COVID-19 older than 40 years (FC = 2.17 ; p = 0.03) and the age of 50 years (FC = 2.15; p = 0.04). Our MR analysis revealed that AMD risk derives from complement system dysfunction {OR (95% CI); hospitalization = 1.02 (1.01–1.03), infection = 1.02 (1.01–1.03) and increased levels of the serum cytokine PDGF-BB {β (95% CI); critical illness = 0.07 (0.02–0.11)} are significantly associated with COVID-19 outcomes.

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

title_words_as_hashtags]

Leave a Comment

Your email address will not be published. Required fields are marked *