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Heritability of Protein and Metabolite Biomarkers Associated with COVID-19 Severity: A Metabolomics and Proteomics
Amelia K Haj1, Haytham Hasan1, Thomas J Raife1
1Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 3170 UW Medical Foundation Centennial Building (MFCB), Madison, WI 53705-2281, USA.
Objectives:
Prior studies have characterized protein and metabolite changes associated with SARS-CoV-2 infection; we hypothesized that these biomarkers may be part of heritable metabolic pathways in erythrocytes.
Methods:
Using a twin study of erythrocyte protein and metabolite levels, we describe the heritability of, and correlations among, previously identified biomarkers that correlate with COVID-19 severity. We used gene ontology and pathway enrichment analysis tools to identify pathways and biological processes enriched among these biomarkers.
Results:
Many COVID-19 biomarkers are highly heritable in erythrocytes. Among heritable metabolites downregulated in COVID-19, metabolites involved in amino acid metabolism and biosynthesis are enriched. Specific amino acid metabolism pathways (valine, leucine, and isoleucine biosynthesis; glycine, serine, and threonine metabolism; and arginine biosynthesis) are heritable in erythrocytes.
Conclusions:
Metabolic pathways downregulated in COVID-19, particularly amino acid biosynthesis and metabolism pathways, are heritable in erythrocytes. This finding suggests that a component of the variation in COVID-19 severity may be the result of phenotypic variation in heritable metabolic pathways; future studies will be necessary to determine whether individual variation in amino acid metabolism pathways correlates with heritable outcomes of COVID-19.
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