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Shared genomic architecture between COVID-19 severity and numerous clinical and physiologic parameters revealed by LD score regression analysis.

Publication ,  Journal Article
Byun, J; Han, Y; Walsh, KM; Park, AS; Bondy, ML; Amos, CI
Published in: Sci Rep
February 3, 2022

The COVID-19 pandemic has produced broad clinical manifestations, from asymptomatic infection to hospitalization and death. Despite progress from genomic and clinical epidemiology research, risk factors for developing severe COVID-19 are incompletely understood and identification of modifiable risk factors is desperately needed. We conducted linkage disequilibrium score regression (LDSR) analysis to estimate cross-trait genetic correlation between COVID-19 severity and various polygenic phenotypes. To attenuate the genetic contribution of smoking and BMI, we further conducted sensitivity analyses by pruning genomic regions associated with smoking/BMI and repeating LDSR analyses. We identified robust positive associations between the genetic architecture of severe COVID-19 and both BMI and smoking. We observed strong positive genetic correlation (rg) with diabetes (rg = 0.25) and shortness of breath walking on level ground (rg = 0.28) and novel protective associations with vitamin E (rg = - 0.53), calcium (rg = - 0.33), retinol (rg = - 0.59), Apolipoprotein A (rg = - 0.13), and HDL (rg = - 0.17), but no association with vitamin D (rg = - 0.02). Removing genomic regions associated with smoking and BMI generally attenuated the associations, but the associations with nutrient biomarkers persisted. This study provides a comprehensive assessment of the shared genetic architecture of COVID-19 severity and numerous clinical/physiologic parameters. Associations with blood and plasma-derived traits identified biomarkers for Mendelian randomization studies to explore causality and nominates therapeutic targets for clinical evaluation.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

February 3, 2022

Volume

12

Issue

1

Start / End Page

1891

Location

England

Related Subject Headings

  • Smoking
  • Risk Factors
  • Regression Analysis
  • Phenotype
  • Patient Acuity
  • Nutrients
  • Multifactorial Inheritance
  • Mendelian Randomization Analysis
  • Male
  • Linkage Disequilibrium
 

Citation

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Byun, J., Han, Y., Walsh, K. M., Park, A. S., Bondy, M. L., & Amos, C. I. (2022). Shared genomic architecture between COVID-19 severity and numerous clinical and physiologic parameters revealed by LD score regression analysis. Sci Rep, 12(1), 1891. https://doi.org/10.1038/s41598-022-05832-5
Byun, Jinyoung, Younghun Han, Kyle M. Walsh, Amy S. Park, Melissa L. Bondy, and Christopher I. Amos. “Shared genomic architecture between COVID-19 severity and numerous clinical and physiologic parameters revealed by LD score regression analysis.Sci Rep 12, no. 1 (February 3, 2022): 1891. https://doi.org/10.1038/s41598-022-05832-5.
Byun, Jinyoung, et al. “Shared genomic architecture between COVID-19 severity and numerous clinical and physiologic parameters revealed by LD score regression analysis.Sci Rep, vol. 12, no. 1, Feb. 2022, p. 1891. Pubmed, doi:10.1038/s41598-022-05832-5.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

February 3, 2022

Volume

12

Issue

1

Start / End Page

1891

Location

England

Related Subject Headings

  • Smoking
  • Risk Factors
  • Regression Analysis
  • Phenotype
  • Patient Acuity
  • Nutrients
  • Multifactorial Inheritance
  • Mendelian Randomization Analysis
  • Male
  • Linkage Disequilibrium