Genetic variation associated with circulating monocyte count in the eMERGE Network

Area of Science:

• Genetics
• Immunology
• Cardiovascular Disease

Background:

• Monocyte count is a risk factor for chronic inflammatory diseases.
• Monocytes are crucial in vascular diseases like atherosclerosis.
• Genetic factors influencing monocyte count are key to understanding disease pathways.

Purpose of the Study:

• Identify genetic variants associated with monocyte count.
• Investigate novel candidate genes and pathways related to monocyte levels.
• Stratify genetic associations by ancestry.

Main Methods:

• Joint and ancestry-stratified genome-wide association analyses.
• Analysis of 11,014 subjects from the electronic Medical Records and Genomics Network.
• Identification of novel and replicated genetic associations.

Main Results:

• Novel associations found in interferon regulatory factor 8 (IRF8) and chemokine-binding protein 2 (CCBP2) genes.
• Replicated associations in ribophorin I (RPN1) and integrin, alpha 4 genes.
• Identified a novel association in the prostaglandin reductase 1 gene.

Conclusions:

• The study identified significant genetic associations with monocyte count, including novel variants in IRF8, CCBP2, and prostaglandin reductase 1.
• Replicated associations in RPN1 and integrin, alpha 4 further support genetic links to monocyte levels.
• These findings enhance understanding of genetic regions influencing monocyte count and their role in inflammatory and vascular diseases.