Transdiagnostic Links Between Depression, Eating Behaviours, and Sleep: Phenotypic and Genetic Insights from the UK Biobank

BackgroundEating behaviour and sleep changes are core diagnostic features of depression, contributing to the heterogeneity of symptoms. Depression demonstrates substantial phenotypic and genetic overlap with sleep disturbances and eating behaviours, yet previous genetic research has predominantly examined these relationships at the disorder level rather than investigating specific symptom patterns. MethodsWorst-episode depression symptoms and core eating behaviours from the UK Biobanks second Mental Health Questionnaire were investigated to uncover the underlying factor structure, indicating latent variables describing symptom clusters (i.e., weight/appetite, emotional symptoms, sleep disturbances). Genome-wide association studies were run for the derived latent variables. Linkage disequilibrium score regression estimated single nucleotide polymorphism heritability and genetic correlations between the latent variables and with other relevant psychiatric and metabolic phenotypes. ResultsA four-factor model best fit the data, identifying the symptom clusters of (1) increased appetite/weight (including binge eating), (2) fatigue/anhedonia, (3) decreased appetite/weight, and (4) negative self-perception. The two appetite/weight factors were negatively correlated both phenotypically and genetically, indicating distinct symptom pathways. Factor SNP-based heritabilities were around 6%, and GWAS identified one associated SNP in the FTO gene for increased appetite/weight. Genetic correlation analyses revealed distinct patterns across BMI, sleep traits (e.g., insomnia, short sleep), and psychiatric conditions, including PTSD and anxiety. ConclusionsThese findings demonstrate the multidimensional and heterogeneous nature of depression at both phenotypic and genetic levels and provide evidence for subtyping of depression. Symptom-level analyses provide valuable insight into the complex aetiology of depression.