Polygenic Risk Links to the Gut Microbiome: The MAGI Catalog

Abstract

Polygenic risk scores (PRSs) can effectively identify individuals at risk across various health conditions, yet their association with the gut microbiome remains uncharacterized. We systematically analyzed associations between 4,794 PRSs covering 615 traits and diseases and the gut microbiome within the Estonian Microbiome Cohort (N > 2,500). Microbiome diversity was associated with 62 distinct PRSs across 10 traits, indicating that genetic predisposition is linked to significant alterations in the microbiome composition. At the species level, 282 associations were identified across 100 PRSs for 34 traits, with triglyceride measurements, glucose regulation, and chronotype measurement PRSs showing the strongest signals. Mediation analysis suggests that the microbiome is altered by physiological changes linked to genetic risk but can also mediate this risk. These results help define early microbial biomarkers and explain inter-individual variability. The findings are accessible through the interactive Microbiome And Genomic Interaction (MAGI) Catalog to support future research.