A shared genetic contribution to osteoarthritis and COVID-19 outcomes: a large-scale genome-wide cross-trait analysis

Yi-Xuan Huang; Tian Tian; Ji-Xiang Huang; Jing Wang; Cong Sui; Jing Ni

doi:10.3389/fimmu.2023.1184958

A shared genetic contribution to osteoarthritis and COVID-19 outcomes: a large-scale genome-wide cross-trait analysis

Front Immunol. 2023 Jun 16:14:1184958. doi: 10.3389/fimmu.2023.1184958. eCollection 2023.

Authors

Yi-Xuan Huang^{1

2}, Tian Tian¹, Ji-Xiang Huang¹, Jing Wang¹, Cong Sui³, Jing Ni¹

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
² Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
³ Department of Orthopedics Trauma, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Abstract

Background: Patients with osteoarthritis (OA) are exposed to an increased risk of adverse outcomes of COVID-19, and they tend to experience disruption in access to healthcare services and exercise facilities. However, a deep understanding of this comorbidity phenomenon and the underlying genetic architecture of the two diseases is still unclear. In this study, we aimed to untangle the relationship between OA and COVID-19 outcomes by conducting a large-scale genome-wide cross-trait analysis.

Methods: Genetic correlation and causal relationships between OA and COVID-19 outcomes (critical COVID-19, COVID-19 hospitalization, and COVID-19 infection) were estimated by linkage disequilibrium score regression and Mendelian Randomization approaches. We further applied Multi-Trait Analysis of GWAS and colocalization analysis to identify putative functional genes associated with both OA and COVID-19 outcomes.

Results: Significant positive genetic correlations between OA susceptibility and both critical COVID-19 (r_g=0.266, P=0.0097) and COVID-19 hospitalization (r_g=0.361, P=0.0006) were detected. However, there was no evidence to support causal genetic relationships between OA and critical COVID-19 (OR=1.17[1.00-1.36], P=0.049) or OA and COVID-19 hospitalization OR=1.08[0.97-1.20], P=0.143). These results were robustly consistent after the removal of obesity-related single nucleotide polymorphisms (SNPs). Moreover, we identified a strong association signal located near the FYCO1 gene (lead SNPs: rs71325101 for critical COVID-19, P_meta=1.02×10^-34; rs13079478 for COVID-19 hospitalization, P_meta=1.09×10^-25).

Conclusion: Our findings further confirmed the comorbidity of OA and COVID-19 severity, but indicate a non-causal impact of OA on COVID-19 outcomes. The study offers an instructive perspective that OA patients did not generate negative COVID-19 outcomes during the pandemic in a causal way. Further clinical guidance can be formulated to enhance the quality of self-management in vulnerable OA patients.

Keywords: COVID-19 severity; Mendelian randomization; cross-trait analysis; genetic correlation; osteoarthritis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19* / genetics
Exercise
Hospitalization
Humans
Linkage Disequilibrium
Osteoarthritis* / epidemiology
Osteoarthritis* / genetics

Grants and funding

This research was funded by Anhui Provincial Natural Science Foundation (2108085QH361), Natural Science Foundation of Anhui Medical University (2020xkj011), Undergraduate Scientific Research Training Project of Anhui Medical University (2021-ZQKY-45), Fundamental and Clinical Research Collaboration Project of Anhui Medical University (2022xkjT019) and Postdoctoral Research Start-up Foundation of The First Affiliated Hospital of Anhui Medical University (BSKY2022061).