Functionally enriched human polymorphisms associate to species in the chronic wound microbiome.

Abstract

Chronic wounds are a burden to millions of patients worldwide and impaired wound closure has been shown to be associated with wound microbiota. Recent evidence suggests human genetics may shape differences in composition of wound microbiomes. Here, a microbiome genome-wide association study was used to test effects of human genetics on the relative abundances of bacterial species in chronic wounds. Sixteen species were associated with 193 genetic loci distributed across 25 non-overlapping genomic regions, with per-species heritability estimates ranging up to 20%. Functional analyses on genomic regions and species resulted in overrepresentation of pathways relevant to microbial infection and wound healing. Species associated with host genetics exhibited co-occurrence relationships with common wound pathogens including Staphylococcus aureus. Moreover, the genetic distance among patients was significantly related to differences in their overall wound microbiome composition. Identification of genetic biomarkers reveals predictive risk factors and new mechanistic insight for chronic wounds.