Using major depression polygenic risk scores to explore the depressive symptom continuum. Issue 1 (10th January 2022)

• Record Type: Journal Article
• Authors: Jermy, Bradley S.; Hagenaars, Saskia P.; Glanville, Kylie P.; Coleman, Jonathan R. I.; Howard, David M.; Breen, Gerome; Vassos, Evangelos; Lewis, Cathryn M.
• Is Part Of: Psychological medicine. Volume 52:Issue 1(2022)
• Page Start: 149
• Page End: 158
• Publication Date: 2022-01-10
• Subjects: Categorical -- dimensional -- genetics -- major depression -- polygenic risk scores -- psychiatric nosology; Psychiatry -- Periodicals; Medicine and psychology -- Periodicals; Clinical psychology -- Periodicals; 616.89
• DOI: 10.1017/S0033291720001828
• Languages: English
• ISSNs: 0033-2917

Abstract

Abstract: Background: Major 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. Methods: Factor 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). Results: Confirmatory 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- and 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 ). Conclusions: An association between MD PRS and a continuous phenotype of depressive symptoms in case- and 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.