Dissecting the Causal Association Between Bulimia Nervosa and Structural Brain Abnormalities: A Two-Sample Bidirectional Mendelian Randomization Study

Abstract

Background

Diverse correlations between structural brain abnormalities and the clinical feature of bulimia nervosa (BN) have been identified in previous observational studies.

Objective

To explore the bidirectional causality between BN and brain structural magnetic resonance imaging (MRI) phenotypes.

Methods

Genome-wide association studies (GWAS) of 2441 participants identified genetic variants associated with disordered eating and predicted BN, whereas UK Biobank 3D-T1 MRI data were used to analyze brain structural phenotypes. A bidirectional two-sample Mendelian randomization (MR) approach was used to investigate the causal relationships between BN and brain structural traits.

Results

The forward MR analysis showed that BN exerted a significant causal effect on decreased volume of left nucleus accumbens area (NAc), decreased surface area (SA) of left inferior temporal gyrus, and increased cortical thickness (CT) of left planum temporale and right inferior temporal gyrus. In the reverse MR analysis, we found that right putamen volume, left hippocampus volume, and right planum temporale gyrus CT were positively associated with BN risk. Besides, SA of right inferior temporal gyrus and left lateral orbital gyrus and CT of left superior occipital gyrus were inversely correlated with BN risk.

Conclusion

Our findings confirmed the potential causal effects of BN on brain structure changes involving multiple functional regions and identified that genetically determined variation in specific brain structural regions could be causal for BN to some extent.