A Predictive Model for Anemia and Coronary Heart Disease Based on Bidirectional Two-Sample Mendelian Randomization...

Area of Science:

• Cardiovascular Research
• Hematology
• Genetics and Genomics

Background:

• Anemia is associated with increased coronary heart disease (CHD) risk, but the causal link is not fully understood.
• Investigating the bidirectional relationship between anemia and CHD is crucial for understanding disease mechanisms.

Purpose of the Study:

• To elucidate the causal associations between different types of anemia and coronary heart disease (CHD).
• To identify potential molecular biomarkers for early detection and understanding of CHD in anemic patients.

Main Methods:

• Mendelian Randomization (MR) analysis using large biobank and gene expression data.
• Integrated bioinformatics including differential expression, weighted gene co-expression network analysis (WGCNA), and machine learning (LASSO, RF, SVM).
• In vitro validation using an oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell model and western blot.

Main Results:

• MR analysis confirmed a positive causal link between vitamin B12 deficiency anemia and hemolytic anemia with CHD.
• Six core genes related to immune response, inflammation, and lipid metabolism were identified.
• IFIH1 and APBB2 were identified as key diagnostic biomarkers, with altered expression observed in vitro, and affected immune cell infiltration (macrophages, mast cells, T cells) was noted.

Conclusions:

• This study establishes the causal role of vitamin B12 deficiency anemia and hemolytic anemia in CHD development.
• IFIH1 and APBB2 are proposed as novel biomarkers for CHD.
• Findings provide a foundation for understanding the molecular links between anemia and CHD, aiding in improved clinical early warning systems.