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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 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., cr...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821609/ https://www.ncbi.nlm.nih.gov/pubmed/36614910 http://dx.doi.org/10.3390/jcm12010109 |
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author | Chung, Jaeyoon Vig, Viha Sun, Xinyu Han, Xudong O’Connor, George T. Chen, Xuejing DeAngelis, Margaret M. Farrer, Lindsay A. Subramanian, Manju L. |
author_facet | Chung, Jaeyoon Vig, Viha Sun, Xinyu Han, Xudong O’Connor, George T. Chen, Xuejing DeAngelis, Margaret M. Farrer, Lindsay A. Subramanian, Manju L. |
author_sort | Chung, Jaeyoon |
collection | PubMed |
description | Age-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 (r(G) = 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. |
format | Online Article Text |
id | pubmed-9821609 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98216092023-01-07 Genome-Wide Pleiotropy Study Identifies Association of PDGFB with Age-Related Macular Degeneration and COVID-19 Infection Outcomes Chung, Jaeyoon Vig, Viha Sun, Xinyu Han, Xudong O’Connor, George T. Chen, Xuejing DeAngelis, Margaret M. Farrer, Lindsay A. Subramanian, Manju L. J Clin Med Article Age-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 (r(G) = 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. MDPI 2022-12-23 /pmc/articles/PMC9821609/ /pubmed/36614910 http://dx.doi.org/10.3390/jcm12010109 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chung, Jaeyoon Vig, Viha Sun, Xinyu Han, Xudong O’Connor, George T. Chen, Xuejing DeAngelis, Margaret M. Farrer, Lindsay A. Subramanian, Manju L. Genome-Wide Pleiotropy Study Identifies Association of PDGFB with Age-Related Macular Degeneration and COVID-19 Infection Outcomes |
title | Genome-Wide Pleiotropy Study Identifies Association of PDGFB with Age-Related Macular Degeneration and COVID-19 Infection Outcomes |
title_full | Genome-Wide Pleiotropy Study Identifies Association of PDGFB with Age-Related Macular Degeneration and COVID-19 Infection Outcomes |
title_fullStr | Genome-Wide Pleiotropy Study Identifies Association of PDGFB with Age-Related Macular Degeneration and COVID-19 Infection Outcomes |
title_full_unstemmed | Genome-Wide Pleiotropy Study Identifies Association of PDGFB with Age-Related Macular Degeneration and COVID-19 Infection Outcomes |
title_short | Genome-Wide Pleiotropy Study Identifies Association of PDGFB with Age-Related Macular Degeneration and COVID-19 Infection Outcomes |
title_sort | genome-wide pleiotropy study identifies association of pdgfb with age-related macular degeneration and covid-19 infection outcomes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821609/ https://www.ncbi.nlm.nih.gov/pubmed/36614910 http://dx.doi.org/10.3390/jcm12010109 |
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