Summary: More severe COVID-19 findings associated with age-related macular degeneration likely result 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 an increased risk of infection and mortality. AMD has been reported to confer a higher risk of serious complications from SARS-CoV-2 infection, including respiratory failure and death (25%), a higher risk than type 2 diabetes ( 21%) and obesity (13%).
Given these observations, researchers at Boston University’s 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 the PDGFB embarrassed. This gene codes for 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 findings were associated with AMD likely resulting from a genetic predisposition to dysfunction involving complement proteins, as well as a higher blood serum level of Pdgf.
“Our findings add to the body of evidence of increased risk of infection and mortality from COVID-19 in 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-corresponding author Lindsay A. Farrer, PhD, Chief of the Department 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 COVID-19 outcomes (infection rate, severe illness and hospitalization) using large genetic datasets containing tens of thousands of individuals. These datasets were previously assembled 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 AMD or COVID-19 patients and control groups to assess the association of variants in PDGFB with gene activity.
Finally, they used an analytical technique that allowed them to study the causal relationships between PDGFB genetic variants, blood Pdgfb concentration, AMD and COVID-19 outcomes.
According to the researchers, these results suggest that the reduction PDGFB gene activity and serum PDGF concentration may reduce the severity of COVID-19, especially in the elderly.
“Therapeutic strategies combining anti-VEGF therapy (a current AMD treatment 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 were considered even more effective than VEGF alone treatment and are currently being studied 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 the pathology and shared risk factors that contribute to worse clinical outcomes in both states. pathological.
Funding: 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: Image is in public domain
See also
Original research: Free access.
“Genome-wide pleiotropy study identifies association of PDGFB with age-related macular degeneration and COVID-19 infection outcomes” by Lindsay A. Farrer et al. Journal of Clinical Medicine
Abstract
Genome-wide pleiotropy study identifies association of PDGFB with age-related macular degeneration and COVID-19 infection outcomes
Age-related macular degeneration (AMD) has been implicated as a risk factor for serious consequences of COVID-19.
We assessed the shared genetic architecture between AMD and COVID-19 (severe illness, hospitalization, and infections) using genetic correlation and pleiotropy analyzes (i.e. meta-analysis crossover phenotype) AMD (not = 33,976) and COVID-19 (not ≥ 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 (rg = 0.10, p = 0.02) and identified new significant genome-wide associations PDGFB (best SNP: rs130651; p = 2.4 × 10−8) in the analysis of the pleiotropy 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 (best eQTL p = 7.1 × 10−20 in T cells). PDGFB expression was observed to be higher in AMD cases than in AMD controls {factor change (FC) = 1.02; p = 0.067}, as well as at peak stage of COVID-19 symptoms (11-20 days after symptom onset) versus early/progressive stage (0-10 days) in COVID-19 patients older than 40 years (HR = 2.17; p = 0.03) and 50 years (CF = 2.15; p = 0.04). Our RM analysis revealed that responsibility for AMD risk stemmed from dysfunction of the complement system {OR (95% CI); hospitalization = 1.02 (1.01–1.03), infection = 1.02 (1.01–1.03) and increased serum levels of PDGF-BB cytokine {β (95% CI); severe disease = 0.07 (0.02–0.11)} are significantly associated with COVID-19 outcomes.
Our study demonstrated that responsibility for AMD is associated with an increased risk of COVID-19, and PDGFB may be responsible for the severe consequences of COVID-19 in patients with AMD.
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