Gut fungi are associated with human genetic variation and disease risk.

Emily P Van Syoc; Emily R Davenport; Seth R Bordenstein

doi:10.1371/journal.pbio.3003339

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Gut fungi are associated with human genetic variation and disease risk.

Emily P Van Syoc·Emily R Davenport·Seth R Bordenstein

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Abstract

Human genetic determinants of the gut mycobiome remain uninvestigated despite decades of research highlighting tripartite relationships between gut bacteria, genetic background, and disease. Here, we present the first genome-wide association study on the number and types of human genetic loci influencing gut fungi relative abundance. We detect 148 fungi-associated variants (FAVs) across 7 chromosomes that statistically associate with 9 fungal taxa. Of these FAVs, several occur in the protein-coding genes PTPRC, ANAPC10, NAV2, and CDH13. Additional FAVs link to tissue-specific gene expression as fungi-associated expression quantitative trait loci. Notably, the relative abundance of gut yeast Kazachstania associates with genetic variation in CDH13 encoding T-cadherin, a protein linked to cardiovascular disease. Kazachstania forms a causal relationship with cardiovascular disease risk in a mendelian two-sample randomization analysis. These findings establish previously unrecognized connections between human genetics, gut fungi, and chronic disease, broadening the paradigm of human-microbe interactions in the gut to the mycobiome.

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Humans Genome-Wide Association Study Genetic Variation Gastrointestinal Microbiome Fungi Genetic Predisposition to Disease Cardiovascular Diseases Quantitative Trait Loci Cadherins Mycobiome Polymorphism, Single Nucleotide Journal Article Research Support, N.I.H., Extramural

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Emily P Van Syoc, Emily R Davenport, Seth R Bordenstein. 2025-09-02. Gut fungi are associated with human genetic variation and disease risk.. https://doi.org/10.1371/journal.pbio.3003339

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