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Causal association between 731 immunocyte phenotypes and liver cirrhosis: A bidirectional two-sample mendelian
Ying Li1, Xin Quan1, Yang Tai1
1Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
Insights
This study used Mendelian randomization to investigate immune cell phenotypes and liver cirrhosis, finding concrete causal links. These discoveries may guide new liver cirrhosis treatments.
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.
Background:
Liver cirrhosis is a progressive hepatic disease whose immunological basis has attracted increasing attention. However, it remains unclear whether a concrete causal association exists between immunocyte phenotypes and liver cirrhosis.
Aim:
To explore the concrete causal relationships between immunocyte phenotypes and liver cirrhosis through a mendelian randomization (MR) study.
Methods:
Data on 731 immunocyte phenotypes were obtained from genome-wide association studies. Liver cirrhosis data were derived from the Finn Gen dataset, which included 214403 individuals of European ancestry. We used inverse variable weighting as the primary analysis method to assess the causal relationship. Sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.
Results:
The MR analysis demonstrated that 11 immune cell phenotypes have a positive association with liver cirrhosis [P < 0.05, odds ratio (OR) > 1] and that 9 immunocyte phenotypes were negatively correlated with liver cirrhosis (P < 0.05, OR < 1). Liver cirrhosis was positively linked to 9 immune cell phenotypes (P < 0.05, OR > 1) and negatively linked to 10 immune cell phenotypes (P < 0.05; OR < 1). None of these associations showed heterogeneity or horizontally pleiotropy (P > 0.05).
Conclusion:
This bidirectional two-sample MR study demonstrated a concrete causal association between immunocyte phenotypes and liver cirrhosis. These findings offer new directions for the treatment of liver cirrhosis.
Related Concept Videos
01:23Cirrhosis I: Introduction
01:24Cirrhosis II: Pathophysiology