Postpartum and non-postpartum depression: a population-based matched case-control study comparing polygenic risk scores for severe mental disorders

Trine Munk-Olsen, Arianna Di Florio, Kathrine B. Madsen, Clara Albiñana, Merete L. Mægbæk, Veerle Bergink, Vibe G. Frøkjær, Esben Agerbo, Bjarni J. Vilhjálmsson, Thomas Werge, Merete Nordentoft, David M. Hougaard, Anders D. Børglum, Ole Mors, Preben Bo Mortensen, Xiaoqin Liu*


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It remains inconclusive whether postpartum depression (PPD) and depression with onset outside the postpartum period (MDD) are genetically distinct disorders. We aimed to investigate whether polygenic risk scores (PGSs) for major mental disorders differ between PPD cases and MDD cases in a nested case-control study of 50,057 women born from 1981 to 1997 in the iPSYCH2015 sample in Demark. We identified 333 women with first-onset postpartum depression (PPD group), who were matched with 993 women with first-onset depression diagnosed outside of postpartum (MDD group), and 999 female population controls. Data on genetics and depressive disorders were retrieved from neonatal biobanks and the Psychiatric Central Research Register. PGSs were calculated from both individual-level genetic data and meta-analysis summary statistics from the Psychiatric Genomics Consortium. Conditional logistic regression was used to calculate the odds ratio (OR), accounting for the selection-related reproductive behavior. After adjustment for covariates, higher PGSs for severe mental disorders were associated with increased ORs of both PPD and MDD. Compared with MDD cases, MDD PGS and attention-deficit/hyperactivity disorder PGS were marginally but not statistically higher for PPD cases, with the OR of PPD versus MDD being 1.12 (95% CI: 0.97–1.29) and 1.11 (0.97–1.27) per-standard deviation increase, respectively. The ORs of PPD versus MDD did not statistically differ by PGSs of bipolar disorder, schizophrenia, or autism spectrum disorder. Our findings suggest that relying on PGS data, there was no clear evidence of distinct genetic make-up of women with depression occurring during or outside postpartum, after taking the selection-related reproductive behavior into account.

TidsskriftTranslational Psychiatry
Antal sider7
StatusUdgivet - 13. nov. 2023

Bibliografisk note

Funding Information:
The authors gratefully acknowledge the Psychiatric Genomics Consortium (PGC) and the research participants and employees of 23andMe, Inc., for providing the summary statistics used to generate the polygenic risk scores. TMO and VB are supported by the National Institute of Mental Health (NIMH) (R01MH122869). TMO is also supported by the Lundbeck Foundation (R313-2019-569), and AUFF NOVA (AUFF-E 2016-9-25). EA, TW, MN, DMH, ADB, OM, and PBM are supported by iPSYCH, the Lundbeck Foundation Initiative for Integrative Psychiatric Research (R102-A9118, R155-2014-1724, and R248-2017-2003), and the Universities and University Hospitals of Aarhus and Copenhagen. The Danish National Biobank resource was supported by the Novo Nordisk Foundation. High-performance computer capacity for handling and statistical analysis of iPSYCH data on the Genome DK HPC facility was provided by the Center for Genomics and Personalized Medicine and the Center for Integrative Sequencing, iSEQ, Aarhus University, Denmark (grant to ADB). XL was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 891079. The funders had no role in the study design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.


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