Extensive Mendelian randomization study identifies potential causal risk factors for severe COVID-19

Yitang Sun; Jingqi Zhou; Kaixiong Ye

doi:10.1038/s43856-021-00061-9

Extensive Mendelian randomization study identifies potential causal risk factors for severe COVID-19

Commun Med (Lond). 2021 Dec 9:1:59. doi: 10.1038/s43856-021-00061-9. eCollection 2021.

Authors

Yitang Sun¹, Jingqi Zhou^{1

2}, Kaixiong Ye^{1

3}

Affiliations

¹ Department of Genetics, Franklin College of Arts and Sciences, University of Georgia, Athens, GA USA.
² School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Institute of Bioinformatics, University of Georgia, Athens, GA USA.

Abstract

Background: Identifying causal risk factors for severe coronavirus disease 2019 (COVID-19) is critical for its prevention and treatment. Many associated pre-existing conditions and biomarkers have been reported, but these observational associations suffer from confounding and reverse causation.

Methods: Here, we perform a large-scale two-sample Mendelian randomization (MR) analysis to evaluate the causal roles of many traits in severe COVID-19.

Results: Our results highlight multiple body mass index (BMI)-related traits as risk-increasing: BMI (OR: 1.89, 95% CI: 1.51-2.37), hip circumference (OR: 1.46, 1.15-1.85), and waist circumference (OR: 1.82, 1.36-2.43). Our multivariable MR analysis further suggests that the BMI-related effect might be driven by fat mass (OR: 1.63, 1.03-2.58), but not fat-free mass (OR: 1.00, 0.61-1.66). Several white blood cell counts are negatively associated with severe COVID-19, including those of neutrophils (OR: 0.76, 0.61-0.94), granulocytes (OR: 0.75, 0.601-0.93), and myeloid white blood cells (OR: 0.77, 0.62-0.96). Furthermore, some circulating proteins are associated with an increased risk of (e.g., zinc-alpha-2-glycoprotein) or protection from severe COVID-19 (e.g., prostate-associated microseminoprotein).

Conclusions: Our study suggests that fat mass and white blood cells might be involved in the development of severe COVID-19. It also prioritizes potential risk and protective factors that might serve as drug targets and guide the effective protection of high-risk individuals.

Keywords: Epidemiology; Genetic association study.