COVID-19 susceptibility variants associate with blood clots, thrombophlebitis and circulatory diseases

PLoS One. 2021 Sep 3;16(9):e0256988. doi: 10.1371/journal.pone.0256988. eCollection 2021.

Abstract

Epidemiological studies suggest that individuals with comorbid conditions including diabetes, chronic lung, inflammatory and vascular disease, are at higher risk of adverse COVID-19 outcomes. Genome-wide association studies have identified several loci associated with increased susceptibility and severity for COVID-19. However, it is not clear whether these associations are genetically determined or not. We used a Phenome-Wide Association (PheWAS) approach to investigate the role of genetically determined COVID-19 susceptibility on disease related outcomes. PheWAS analyses were performed in order to identify traits and diseases related to COVID-19 susceptibility and severity, evaluated through a predictive COVID-19 risk score. We utilised phenotypic data in up to 400,000 individuals from the UK Biobank, including Hospital Episode Statistics and General Practice data. We identified a spectrum of associations between both genetically determined COVID-19 susceptibility and severity with a number of traits. COVID-19 risk was associated with increased risk for phlebitis and thrombophlebitis (OR = 1.11, p = 5.36e-08). We also identified significant signals between COVID-19 susceptibility with blood clots in the leg (OR = 1.1, p = 1.66e-16) and with increased risk for blood clots in the lung (OR = 1.12, p = 1.45 e-10). Our study identifies significant association of genetically determined COVID-19 with increased blood clot events in leg and lungs. The reported associations between both COVID-19 susceptibility and severity and other diseases adds to the identification and stratification of individuals at increased risk, adverse outcomes and long-term effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / epidemiology
  • COVID-19 / genetics*
  • COVID-19 / virology
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / virology
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mendelian Randomization Analysis
  • Obesity / epidemiology
  • Obesity / genetics*
  • Obesity / virology
  • Phenomics
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • SARS-CoV-2 / pathogenicity
  • Thrombophlebitis / epidemiology
  • Thrombophlebitis / genetics*
  • Thrombophlebitis / virology
  • Thrombosis / epidemiology
  • Thrombosis / genetics*
  • Thrombosis / virology