Circulating inflammatory proteins and osteomyelitis: A bidirectional Mendelian randomization and colocalization...

Area of Science:

• Immunology
• Genetics
• Orthopedics

Background:

• Circulating inflammatory proteins (CIPs) are linked to osteomyelitis (OM) progression, but their causal role is uncertain.
• Understanding these relationships is crucial for developing effective treatments for OM.

Purpose of the Study:

• To investigate the potential causal relationships between CIPs and OM using a bidirectional 2-sample Mendelian randomization (MR) approach.
• To identify specific CIPs that may be causal factors in OM development.

Main Methods:

• Utilized genome-wide association study summary statistics for 91 inflammation-related proteins and OM.
• Employed inverse variance weighted (IVW) as the primary MR method, with sensitivity analyses including MR-Egger and weighted median.
• Conducted colocalization and pathway enrichment analyses to identify shared causal variants and biological mechanisms.

Main Results:

• Elevated tumor necrosis factor-beta (TNF-β) levels were associated with increased OM risk (OR=1.132).
• Decreased osteoprotegerin (OR=0.772) and adenosine deaminase (OR=0.811) levels were linked to higher OM risk.
• Reverse MR identified several other inflammatory proteins, including interleukin-10 (IL10), associated with OM susceptibility.

Conclusions:

• Identified TNF-β, osteoprotegerin, and adenosine deaminase as potentially causal factors in osteomyelitis development.
• Highlighted the involvement of Toll-like receptor signaling and T-helper 17 cell differentiation pathways.
• Suggests these CIPs represent promising targets for future immunomodulatory therapies for OM.