Lipids & metabolic liver disease
Causal effect of adiposity on the risk of 19 gastrointestinal diseases: a Mendelian randomization study
Authors' conclusion
High genetically predicted adiposity was causally associated with an increased risk of GI abnormalities, particularly of hepatobiliary organs (liver, biliary tract, and gallbladder) that are functionally related to fat metabolism.
Study context
- Population
- UK Biobank participants, Finnish-descent participants and consortia participants of predominantly European ancestry
- Comparison
- Genetically predicted BMI or waist circumference (WC) and risk of gastrointestinal (GI) diseases
- Outcome
- Risk of GI diseases (causal associations of BMI or WC with GI conditions)
Methodological detailssingle-nucleotide polymorphisms as instrumental variables, multivariable Mendelian randomization
- Single-nucleotide polymorphisms as instrumental variables
- Multivariable Mendelian randomization
Main finding
As reported in the abstract
GI diseases per 1-SD increase in genetically predicted BMI (4.77 kg/m²) or WC (12.52 cm)
Odds ratio (95% CI)P value
BMI per 1-SD increaseNAFLD
1.22(1.12–1.34)
P < 0.0001BMI per 1-SD increasecholecystitis
1.65(1.31–2.06)
P < 0.0001WC per 1-SD increasegastric cancer
1.41(1.17–1.70)
P = 0.0015WC per 1-SD increasecholelithiasis
1.74(1.21–1.78)
P < 0.0001Per 1-SD increase, as printed
Further findings
Alcoholic liver disease and WC, adjusted for alcohol consumption
- Alcoholic liver disease consistently associated with WC even after adjusting for alcohol consumption
- Multivariable Mendelian randomization analysis
Original publication
Causal effect of adiposity on the risk of 19 gastrointestinal diseases: a Mendelian randomization study. Obesity (Silver Spring). Published 4 April 2023. doi:10.
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