| Title: | Using major depression polygenic risk scores to explore the depressive symptom continuum |
| Journal: | Psychological Medicine |
| Published: | 10 Jun 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32519625/ |
| DOI: | https://doi.org/10.1017/s0033291720001828 |
| URL: | https://www.biorxiv.org/content/biorxiv/early/2020/02/26/2020.02.25.962704.full.pdf |
| Citations: | 9 (3 in last 2 years) as of 8 Aug 2024 |
Publication 5965
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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.</p>
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).</p>
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).</p>
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.</p>
6 Keywords
- Depression
- Depressive Disorder, Major
- Humans
- Multifactorial Inheritance
- Patient Health Questionnaire
- Risk Factors
8 Authors
- Bradley S. Jermy
- Saskia P. Hagenaars
- Kylie P. Glanville
- Jonathan R. I. Coleman
- David M. Howard
- Gerome Breen
- Evangelos Vassos
- Cathryn M. Lewis
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