Causal association between 731 immunocyte phenotypes and liver cirrhosis: A bidirectional two-sample mendelian...

Area of Science:

• Immunology
• Genetics
• Hepatology

Background:

• Liver cirrhosis is a progressive liver disease with growing interest in its immunological underpinnings.
• A clear causal link between immune cell phenotypes and liver cirrhosis remains to be established.

Purpose of the Study:

• To investigate the causal relationships between immunocyte phenotypes and liver cirrhosis using a Mendelian randomization (MR) approach.

Main Methods:

• Utilized genome-wide association study data for 731 immunocyte phenotypes.
• Employed a bidirectional two-sample MR study design with data from the FinnGen dataset (214,403 individuals).
• Inverse variable weighting was the primary analysis method, with sensitivity analyses for heterogeneity and pleiotropy.

Main Results:

• Identified 11 immunocyte phenotypes causally associated with increased liver cirrhosis risk (OR > 1).
• Found 9 immunocyte phenotypes causally associated with decreased liver cirrhosis risk (OR < 1).
• Confirmed bidirectional causal associations between liver cirrhosis and 19 distinct immune cell phenotypes, with no significant heterogeneity or pleiotropy.

Conclusions:

• Established concrete causal associations between specific immunocyte phenotypes and liver cirrhosis.
• Findings suggest novel therapeutic targets for liver cirrhosis treatment.