Obesity and risk for liver disease: a two-sample Mendelian randomisation study

Area of Science:

• Hepatology
• Metabolic Disorders
• Genetics

Background:

• Obesity is linked to various liver diseases, but causal relationships remain unclear.
• Understanding these links is crucial for public health and clinical interventions.

Purpose of the Study:

• To investigate the causal effects of obesity on diverse liver diseases using Mendelian randomization.
• To differentiate the impact of general obesity (BMI) versus central obesity (WHRadjBMI) on liver health.

Main Methods:

• Employed two-sample Mendelian randomization (MR) and multivariable MR analyses.
• Utilized large-scale genome-wide association study (GWAS) data for exposures (BMI, WHRadjBMI) and liver outcomes.
• Analyzed associations with non-alcoholic fatty liver disease, liver fibrosis, autoimmune hepatitis, and liver function biomarkers.

Main Results:

• Genetically predicted higher BMI and WHRadjBMI were associated with increased risk of non-alcoholic fatty liver disease and liver fibrosis.
• A higher WHRadjBMI showed associations with elevated biomarkers of lipid accumulation and metabolic dysfunction.
• No significant causal associations were found between obesity metrics and primary biliary cholangitis, liver failure, liver cancer, or viral hepatitis.

Conclusions:

• Obesity, particularly central obesity, plays a causal role in the development of non-alcoholic fatty liver disease and liver fibrosis.
• Obesity independently contributes to impaired liver metabolic function.
• These findings suggest targeted obesity management strategies for preventing specific liver conditions.