Integrative Genomic and Transcriptomic Analysis of Anorexia Nervosa: A Multi-omics Approach to Identify Genetic and Molecular Pathways

Background: Anorexia nervosa (AN) is a complex psychiatric disorder, characterized by extreme food restriction, significant weight loss, and distorted body image perception. Methods: A secondary analysis of previously published genome-wide association study data was conducted, comprising 1033 AN cases and 3733 pediatric controls. Genetic, transcriptomic, and proteomic factors underlying AN were examined, and pathway enrichment analyses were performed. Results: Significant associations were identified with genes including low-density lipoprotein receptor-related protein 2, Netrin-G1, ZNF804B, and VGLL4, which are implicated in neurodevelopment, lipid metabolism, and transcriptional regulation. Pathway enrichment highlighted the involvement of the Hedgehog signaling pathway, cholesterol metabolism, and thyroid hormone synthesis, suggesting a strong metabolic component in AN. In addition, microRNA regulation analysis revealed key epigenetic regulators of AN-associated genes, and proteomic analyses indicated links between these genes and immune system interactions, supporting the role of immune dysregulation in the disorder. Conclusion: The study provides comprehensive insights into the multifactorial nature of AN, identifying genetic and molecular pathways that converge on neuropsychiatric and metabolic processes.