| Title: | Altered Blood Cell Traits Underlie a Major Genetic Locus of Severe COVID-19 |
| Journal: | The Journals of Gerontology Series A |
| Published: | 2 Feb 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33530099/ |
| DOI: | https://doi.org/10.1093/gerona/glab035 |
| URL: | https://academic.oup.com/biomedgerontology/article-pdf/76/8/e147/38938626/glab035.pdf |
| Citations: | 14 (5 in last 2 years) as of 8 Aug 2024 |
Publication 4034
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Abstract
BACKGROUND: The genetic locus 3p21.31 has been associated with severe coronavirus disease 2019 (COVID-19), but the underlying pathophysiological mechanism is unknown.</p>
METHODS: To identify intermediate traits associated with the 3p21.31 locus, we first performed a phenome-wide association study (PheWAS) with 923 phenotypes in 310 999 European individuals from the UK Biobank. For genes potentially regulated by the COVID-19 risk variant, we examined associations between their expression and the polygenic score (PGS) of 1263 complex traits in a meta-analysis of 31 684 blood samples. For the prioritized blood cell traits, we tested their associations with age and sex in the same UK Biobank sample.</p>
RESULTS: Our PheWAS highlighted multiple blood cell traits to be associated with the COVID-19 risk variant, including monocyte count and percentage (p = 1.07 × 10-8, 4.09 × 10-13), eosinophil count and percentage (p = 5.73 × 10-3, 2.20 × 10-3), and neutrophil percentage (p = 3.23 × 10-3). The PGS analysis revealed positive associations between the expression of candidate genes and genetically predicted counts of specific blood cells: CCR3 with eosinophil and basophil (p = 5.73 × 10-21, 5.08 × 10-19); CCR2 with monocytes (p = 2.40 × 10-10); and CCR1 with monocytes and neutrophil (p = 1.78 × 10-6, 7.17 × 10-5). Additionally, we found that almost all examined white blood cell traits are significantly different across age and sex groups.</p>
CONCLUSIONS: Our findings suggest that altered blood cell traits, especially those of monocyte, eosinophil, and neutrophil, may represent the mechanistic links between the genetic locus 3p21.31 and severe COVID-19. They may also underlie the increased risk of severe COVID-19 in older adults and men.</p>
12 Keywords
- Aged
- COVID-19
- Female
- Genetic Loci
- Genome-Wide Association Study
- Granulocytes
- Humans
- Leukocyte Count
- Male
- Phenotype
- SARS-CoV-2
- Severity of Illness Index
4 Authors
- Jingqi Zhou
- Yitang Sun
- Weishan Huang
- Kaixiong Ye
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