Identifying the causal relationship between immune factors and osteonecrosis: a two-sample Mendelian randomization...

Area of Science:

• Immunology
• Genetics
• Bone Biology

Background:

• Growing evidence suggests a link between the immune system and osteonecrosis.
• The specific immune factors involved in osteonecrosis pathogenesis are not well understood.

Purpose of the Study:

• To identify causal relationships between immune factors and osteonecrosis using a bidirectional Mendelian randomization approach.
• To explore the genetic underpinnings of immune system involvement in osteonecrosis, including drug-induced cases.

Main Methods:

• Utilized genome-wide association study summary data for a bidirectional Mendelian randomization analysis.
• Applied inverse-variance weighted method and assessed heterogeneity and pleiotropy using Cochrane's Q-test, MR-Egger intercept, MR-PRESSO, and leave-one-out analyses.
• Corrected for false discovery rate to determine significant associations.

Main Results:

• A significant positive correlation was found between the gene-predicted level of CD62L - monocyte %monocyte and osteonecrosis.
• Eight immune traits related to monocytes, dendritic cells, and NK cells showed significant causal effects with drug-induced osteonecrosis.
• Reverse Mendelian randomization analysis did not reveal significant correlations.

Conclusions:

• Provides genetic evidence supporting causal associations between various immune factors and osteonecrosis.
• Highlights the complex interplay between immune and skeletal systems in osteonecrosis development.
• Suggests potential novel therapeutic targets for osteonecrosis by elucidating immune system involvement.