Genomic study identifies immune markers as mediators linking immune and psychiatric disorder genetics

A study published in *PLOS Genetics* by Breunig, Kelly, Schaffer, Lawrence, Lee, Karlson, and Grotzinger investigates the biological mechanisms connecting the genetic risk for immune-mediated diseases with that for psychiatric disorders — a relationship long observed epidemiologically but poorly understood at the molecular level.

Using genomic structural equation modelling applied to genome-wide association study summary statistics, the team examined 11 immune-mediated diseases and 13 psychiatric disorders simultaneously, testing whether 14 immune markers — including C-reactive protein (CRP) and interleukin-6 (IL-6) — mediate the genetic associations between the two disease domains. The modelling approach allows researchers to distinguish shared genetic liability that operates through immune pathways from that which does not, yielding a more mechanistically granular picture than standard genetic correlation analyses.

The results suggest that immune markers do partly mediate cross-domain genetic associations, indicating that the shared genetic signal between, for instance, autoimmune conditions and depression or schizophrenia is in part explained by genetically influenced variation in systemic immune activation. The work has implications for understanding why immune-modulating treatments show some efficacy in psychiatric contexts and for identifying which patients might benefit from immunological approaches. Researchers in psychiatric genetics, immunogenetics, and translational medicine will find the structural modelling methodology of particular interest.