Key result
Genetic liability to very severe COVID-19 was causally associated with an increased risk of coronary heart disease (OR 1.01), with shared genetic variants contributing to the causality.
Why the study?
Comorbidities of COVID-19 and CHD threaten outcomes, but little is known about their shared pathology and genetic variants predisposing to both conditions.
Does genetic predisposition to COVID-19 causally increase the risk of coronary heart disease?
Observational
Mendelian randomization
Yes
Does genetic predisposition to COVID-19 causally increase the risk of coronary heart disease?
Odds Ratio: 1.01 (95% CI 1.01–1.02)
p-value: p=2.2E-14
Genetic predisposition to COVID-19 is a causal risk factor for coronary heart disease, with shared genetic loci (such as ABO and LZTFL1) jointly influencing the risk of both conditions.
Shared genetic signals between COVID-19 severity and CHD may inform risk; leaves open causal validation and clinical utility.
BACKGROUND: Comorbidities of coronavirus disease 2019 (COVID-19)/coronary heart disease (CHD) pose great threats to disease outcomes, yet little is known about their shared pathology. The study aimed to examine whether comorbidities of COVID-19/CHD involved shared genetic pathology, as well as to clarify the shared genetic variants predisposing risks common to COVID-19 severity and CHD risks. METHODS: By leveraging publicly available summary statistics, we assessed the genetically determined causality between COVID-19 and CHD with bidirectional Mendelian randomization. To further quantify the causality contributed by shared genetic variants, we interrogated their genetic correlation with the linkage disequilibrium score regression method. Bayesian colocalization analysis coupled with conditional/conjunctional false discovery rate analysis was applied to decipher the shared causal single nucleotide polymorphisms (SNPs). FINDINGS: Briefly, we observed that the incident CHD risks post COVID-19 infection were partially determined by shared genetic variants. The shared genetic variants contributed to the causality at a proportion of 0.18 (95% CI 0.18-0.19) to 0.23 (95% CI 0.23-0.24). The SNP (rs10490770) located near LZTFL1 suggested direct causality (SNPs → COVID-19 → CHD), and SNPs in ABO (rs579459, rs495828), ILRUN(rs2744961), and CACFD1(rs4962153, rs3094379) may simultaneously influence COVID-19 severity and CHD risks. INTERPRETATION: Five SNPs located near LZTFL1 (rs10490770), ABO (rs579459, rs495828), ILRUN (rs2744961), and CACFD1 (rs4962153, rs3094379) may simultaneously influence their risks. The current study suggested that there may be shared mechanisms predisposing to both COVID-19 severity and CHD risks. Genetic predisposition to COVID-19 is a causal risk factor for CHD, supporting that reducing the COVID-19 infection risk or alleviating COVID-19 severity among those with specific genotypes might reduce their subsequent CHD adverse outcomes. Meanwhile, the shared genetic variants identified may be of clinical implications for identifying the target population who are more vulnerable to adverse CHD outcomes post COVID-19 and may also advance treatments of 'Long COVID-19.'
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Wang et al. (2023) conducted an observational in COVID-19 and Coronary Heart Disease. Genetic liability to very severe COVID-19 vs. General population was evaluated on Coronary heart disease (CHD) risk (OR 1.01, 95% CI 1.01-1.02, p=2.2E-14). Genetic liability to very severe COVID-19 was causally associated with an increased risk of coronary heart disease (OR 1.01), with shared genetic variants contributing to the causality.
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