Anorexia nervosa and gastrointestinal diseases: A multivariable Mendelian randomization study

Area of Science:

• Genetics
• Gastroenterology
• Psychiatry

Background:

• Associations between anorexia nervosa (AN) and gastrointestinal (GI) diseases lack clarity regarding causality.
• Existing research is limited, necessitating further investigation into the bidirectional relationship.

Purpose of the Study:

• To elucidate the causal associations between AN and the risk of developing 24 different GI diseases.
• To employ Mendelian randomization (MR) analyses for robust causal inference.

Main Methods:

• Utilized summary statistics from large genome-wide association studies for AN and GI diseases.
• Performed bidirectional 2-sample MR analyses using genome-wide significant single nucleotide polymorphisms as instrumental variables.
• Conducted multivariable MR analyses adjusting for smoking and alcohol consumption, with inverse-variance weighted method as primary analysis.

Main Results:

• Genetically predicted AN was nominally associated with an increased risk of acute gastritis and Crohn disease.
• Reverse MR analyses indicated a potential positive association between gastric cancer and AN.
• Associations between AN and acute gastritis/Crohn disease persisted after adjusting for lifestyle factors.

Conclusions:

• Provided preliminary genetic evidence supporting a potential causal link between anorexia nervosa and specific GI diseases like acute gastritis and Crohn disease.
• Identified potential targets for future research into the underlying mechanisms and validation of these findings.