Using Major Depression Polygenic Risk Scores to Explore the Depressive Symptom Continuum

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BackgroundMajor depression (MD) is often characterised as a categorical disorder; however, observational studies comparing sub-threshold and clinical depression suggest MD is continuous. Many of these studies do not explore the full continuum and are yet to consider genetics as a risk factor. This study sought to understand if polygenic risk for MD could provide insight into the continuous nature of depression.MethodsFactor analysis on symptom-level data from the UK Biobank (N = 148 957) was used to derive continuous depression phenotypes which were tested for association with polygenic risk scores (PRS) for a categorical definition of MD (N = 119 692).ResultsConfirmatory factor analysis showed a five-factor hierarchical model, incorporating 15 of the original 18 items taken from the PHQ-9, GAD-7 and subjective well-being questionnaires, produced good fit to the observed covariance matrix (CFI = 0.992, TLI = 0.99, RMSEA = 0.038, SRMR = 0.031). MD PRS associated with each factor score (standardised β range: 0.057-0.064) and the association remained when the sample was stratified into case- A nd control-only subsets. The case-only subset had an increased association compared to controls for all factors, shown via a significant interaction between lifetime MD diagnosis and MD PRS (p value range: 2.23 × 10 -3-3.94 × 10 -7).ConclusionsAn association between MD PRS and a continuous phenotype of depressive symptoms in case- A nd control-only subsets provides support against a purely categorical phenotype; indicating further insights into MD can be obtained when this within-group variation is considered. The stronger association within cases suggests this variation may be of particular importance.

Original languageEnglish
JournalPsychological Medicine
Publication statusPublished - 10 Jun 2020


  • Categorical
  • dimensional
  • genetics
  • major depression
  • polygenic risk scores
  • psychiatric nosology


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