Exploring depression treatment response by using polygenic risk scoring across diverse populations
Sandra Lapinska1, Aditya Pimplaskar2, Zhuozheng Shi1
1Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
American Journal of Human Genetics
|June 28, 2025
Summary
Genetic factors influence treatment-resistant depression (TRD). A higher major depression polygenic score (MDD-PGS) is linked to TRD across ancestries, impacting antidepressant response. This study analyzed diverse biobanks for genetic insights.
Area of Science:
- Genetics
- Psychiatry
- Pharmacogenomics
Background:
- Treatment-resistant depression (TRD) affects one-third of major depressive disorder (MDD) patients.
- Genetic overlap between MDD and TRD is noted in European ancestry studies.
- Understanding genetic influences on antidepressant response is crucial for diverse populations.
Purpose of the Study:
- To investigate the association between a major depression polygenic score (MDD-PGS) and TRD.
- To analyze antidepressant response across different genetic ancestries using large biobanks.
- To identify genetic predictors for treatment specificity in MDD.
Main Methods:
- Analysis of two large, diverse biobanks: UCLA ATLAS Community Health Study and All of Us Research Program.
- Calculation and application of a polygenic score for major depression (MDD-PGS).
- Statistical association testing between MDD-PGS and treatment response across various ancestries.
Main Results:
- TRD individuals exhibited higher MDD-PGS compared to treatment responders across all ancestries.
- MDD-PGS significantly predicted selective serotonin reuptake inhibitor (SSRI) response in European and Hispanic/Latin American ancestries.
- Differential MDD-PGS associations were observed for various antidepressant classes (tricyclics, serotonin modulators, SNRIs, atypical agents) across different ancestries.
Conclusions:
- MDD-PGS is a potential biomarker for TRD and antidepressant response across diverse genetic ancestries.
- Genetic insights can inform personalized treatment strategies for MDD.
- Further research in diverse populations is essential for precision psychiatry.
Keywords:
antidepressant responsebiobanksdiverse ancestryelectronic health recordsgeneticsmajor depressive disorderpolygenic risk scorestreatment-related phenotypesMore Related Videos
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