Causal effects of circulating inflammatory proteins on oral phenotypes: Deciphering immune-mediated profiles in the...

Oral manifestations function as precursors to potential systemic pathologies, signaling early indicators of underlying health complications or immunological dysfunctions. Within these dynamics, circulating inflammatory proteins are recognized as critical mediators in immunopharmacology, bridging holistic health, immune response, and oral health.

We employed genetic data from genome-wide association studies to perform comprehensive Mendelian randomization (MR) analyses on 91 circulating inflammatory proteins and 17 oral phenotypes. Six MR algorithms and five auxiliary control measures were utilized to estimate the causal effects. Subsequently, the MR-Bayesian model averaging (MR-BMA) approach was conducted to elucidate the priorities in host-oral communication, followed by network analyses to explore the interactions among phenotypes.

After multiple corrections, MR identified five genetically predicted proteins associated with oral phenotypes. Specifically, FGF21 was correlated with Nteeth and DMFS; hGDNF with gingival pain; CCL4 with stomatitis; and S100A12 with denture use. The causal associations remained robust in sensitivity analyses. Nine protein-phenotype clusters were prioritized using MR-BMA. Among these, S100A12, FGF19, FGF21, and CCL4 exhibited extensive correlations with various oral phenotypes.

Our study offers novel genetic insights into the causal relationships, prioritizations, and connections between circulating inflammatory proteins and oral phenotypes. These findings comprehensively depict immune-mediated proteomic profiles underlying the host-oral axis, providing significant implications for clinical practice, public health, and immunopharmacology.