Genome-wide association studies (GWAS) have identified multiple genetic loci associated with anorexia nervosa (AN); however, the genetic architecture of AN remains largely unknown and many causal genes have not yet been discovered. To prioritize genes associated with AN, we applied metaXcan to integrate summary statistics available from the largest PGC-AN GWAS (3,495 cases and 10,982 controls) with eQTLs (expression quantitative trait loci) of 13 GTEx brain tissues, and identified a total of 133 associations (tagged by 57 unique genes), including multiple potentially promising candidate genes such as SUOX. These identified genes were further validated using an external AN dataset from UK Biobank (770 cases and 135,177 controls) and nine of them were replicated. Moreover, it was found that 72.7% of the identified genes demonstrated pleiotropic effects on at least one of nine other psychiatric disorders. The function analysis revealed these genes were involved in multiple AN-relevant pathways such as synapse organization. Overall, our study identified three candidate genes associated with AN, and would advance our understanding towards the genetic foundation of AN.
Anorexia nervosa, Expression quantitative trait loci, Gene expression, Genome-wide association study, Integrative analysis, Summary statistics