Microbiome-associated human genetic variants impact phenome-wide disease risk

Robert H.George Markowitz, Abigail Leavitt LaBella, Mingjian Shi, Antonis Rokas, John A. Capra, Jane F. Ferguson, Jonathan D. Mosley, Seth R. Bordenstein

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Human genetic variation associates with the composition of the gut microbiome, yet its influence on clinical traits remains largely unknown. We analyzed the consequences of nearly a thousand gut microbiome-associated variants (MAVs) on phenotypes reported in electronic health records from tens of thousands of individuals. We discovered and replicated associations of MAVs with neurological, metabolic, digestive, and circulatory diseases. Five significant MAVs in these categories correlate with the relative abundance of microbes down to the strain level. We also demonstrate that these relationships are independently observed and concordant with microbe by disease associations reported in case-control studies. Moreover, a selective sweep and population differentiation impacted some disease-linked MAVs. Combined, these findings establish triad relationships among the human genome, microbiome, and disease. Consequently, human genetic influences may offer opportunities for precision diagnostics of microbiomeassociated diseases but also highlight the relevance of genetic background for microbiome modulation and therapeutics.

Original languageEnglish (US)
Article numbere2200551119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number26
StatePublished - Jun 28 2022

All Science Journal Classification (ASJC) codes

  • General


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