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Using major depression polygenic risk scores to explore the depressive symptom continuum

Published online by Cambridge University Press:  10 June 2020

Bradley S. Jermy Open the ORCID record for Bradley S. Jermy [Opens in a new window] ,
Saskia P. Hagenaars Open the ORCID record for Saskia P. Hagenaars [Opens in a new window] ,
Kylie P. Glanville Open the ORCID record for Kylie P. Glanville [Opens in a new window] ,
Jonathan R. I. Coleman Open the ORCID record for Jonathan R. I. Coleman [Opens in a new window] ,
David M. Howard Open the ORCID record for David M. Howard [Opens in a new window] ,
Gerome Breen Open the ORCID record for Gerome Breen [Opens in a new window] ,
Evangelos Vassos Open the ORCID record for Evangelos Vassos [Opens in a new window]  and
Cathryn M. Lewis Open the ORCID record for Cathryn M. Lewis [Opens in a new window]
Bradley S. Jermy
Affiliation:
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
Saskia P. Hagenaars
Affiliation:
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
Kylie P. Glanville
Affiliation:
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
Jonathan R. I. Coleman
Affiliation:
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
David M. Howard
Affiliation:
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
Gerome Breen
Affiliation:
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
Evangelos Vassos
Affiliation:
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK
Cathryn M. Lewis*
Affiliation:
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK Department of Medical & Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, London, UK
*
Author for correspondence: Cathryn Lewis, E-mail: cathryn.lewis@kcl.ac.uk
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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.

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.

Keywords

Categoricaldimensionalgeneticsmajor depressionpolygenic risk scorespsychiatric nosology
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 1 , January 2022 , pp. 149 - 158
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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Footnotes

*

These authors share senior authorship.

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