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Genome-Wide Pleiotropy Study Identifies Association of PDGFB with Age-Related Macular Degeneration and COVID-19 Infection OutcomesAge-related macular degeneration (AMD) has been implicated as a risk factor for severe consequences from COVID-19. We evaluated the genetic architecture shared between AMD and COVID-19 (critical illness, hospitalization, and infections) using analyses of genetic correlations and pleiotropy (i.e., cross-phenotype meta-analysis) of AMD (n=33,976) and COVID-19 (n ≥ 1,388,342) and subsequent analyses 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 novel genome-wide significant associations near PDGFB (best SNP: rs130651; p=2.4 × 10−8) in the pleiotropy 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 (best 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 COVID-19 symptom stage (11–20 days after the symptom onset) compared to early/progressive stage (0–10 days) among COVID-19 patients over age 40 (FC=2.17; p=0.03) and age 50 (FC=2.15; p=0.04). Our MR analysis found that the liability of AMD risk derived 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 serum 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 the liability of AMD is associated with an increased risk of COVID-19, and PDGFB may be responsible for the severe COVID-19 outcomes among AMD patients.
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The Glasgow Live quiz that tests your knowledge on famous local sayingsThere are many local phrases and mantras that Glaswegians stick by in everyday life when times get tough - but how many of these sayings can you explain in basic terms?
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Live updates: Shop closures in UK hit highest total for five years\n\t\t\tExpert insights, analysis and smart data help you cut through the noise to spot trends,\n\t\t\trisks and opportunities.\n\t\t\n\t\tJoin over 300,000 Finance professionals who already subscribe to the FT.
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We live on one of the UK's 'cheapest' street - houses cost less than £50kRESIDENTS living on one of the UK’s cheapest streets say they love it there and everyone is friendly. Homes down a small road in Yorkshire are selling for less than £50,000. Despite changing …
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Live updates as Westlink crash causes disruptionIt happened between Broadway and Grosvenor
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