Integrative GWAS Identifies Novel Loci and Genetic Links Between Psychiatric and Metabolic Factors in Anorexia Nervosa

Anorexia nervosa (AN) is a complex psychiatric disorder with both psychiatric and metabolic underpinnings. To explore the genetic architecture of AN, we conducted a meta-analysis of AN GWAS data from European and Finnish populations, identifying a novel genome-wide significant locus near the SOX5 gene. We further integrated GWAS summary statistics from the UK Biobank and FinnGen, focusing on psychiatric traits, metabolic markers, and lifestyle factors. Using cross-trait analysis methods including linkage disequilibrium score regression, Mendelian randomization and multi-trait analysis of GWAS, we revealed the causal relationships between AN and its risk factors, as well as the pleiotropic loci and shared genetic mechanisms. Gene Co-expression Network Analysis further uncovered key gene modules with both metabolic and neurological functions. These findings illustrate the interplay between psychiatric and metabolic pathways, highlighting their collective importance in shaping the genetic architecture of AN.