Polygenic analyses show important differences between MDD symptoms collected using PHQ9 and CIDI-SF

Symptoms of Major Depressive Disorder (MDD) are commonly assessed using self-rating instruments like the Patient Health Questionnaire 9 (PHQ9, for current symptoms), and the Composite International Diagnostic Interview Short-Form (CIDI-SF, for lifetime worst-episode symptoms). Using data from the UKBiobank, we show that corresponding symptoms endorsed through PHQ9 and CIDI-SF have low to moderate genetic correlations (rG=0.43–0.87), and this cannot be fully attributed to different severity thresholds or the use of a skip-structure in CIDI-SF. Through a combination of Mendelian Randomization (MR) and polygenic prediction analyses, we find that PHQ9 symptoms are more associated with traits which reflect general dysphoria, while the skip-structure in CIDI-SF allows for the identification of heterogeneity among likely MDD cases. This has important implications on factor analyses performed on their respective genetic covariance matrices for the purpose of identification of genetic factors behind MDD symptom dimensions and heterogeneity.