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

Area of Science:

• Psychiatry
• Genetics
• Computational Biology

Background:

• Major depression (MD) is often viewed as a distinct disorder, but evidence suggests a continuous spectrum of depressive symptoms.
• Previous studies have not fully explored this continuum or integrated genetic risk factors.

Purpose of the Study:

• To investigate if polygenic risk scores (PRS) for MD can elucidate the continuous nature of depression.
• To examine the association between genetic predisposition to MD and continuous depression phenotypes.

Main Methods:

• Utilized factor analysis on UK Biobank data (N=148,957) to define continuous depression phenotypes.
• Tested associations between these phenotypes and PRS for MD (N=119,692).
• Employed a five-factor hierarchical model derived from PHQ-9, GAD-7, and well-being questionnaires.

Main Results:

• A five-factor model demonstrated good fit to the data.
• MD PRS significantly associated with all derived continuous depression factors (standardized β range: 0.057-0.064).
• This association persisted in case- and control-only subsets, with stronger effects in cases (significant interaction).

Conclusions:

• Findings support a continuous model of depressive symptoms, challenging a purely categorical view of MD.
• Polygenic risk for MD is associated with continuous symptom variation.
• The heightened association within MD cases highlights the clinical relevance of considering symptom heterogeneity.