Transcriptome-wide association study for postpartum depression implicates altered B-cell activation and insulin resistance. Academic Article uri icon


  • Postpartum depression (PPD) affects 1 in 7 women and has negative mental health consequences for both mother and child. However, the precise biological mechanisms behind the disorder are unknown. Therefore, we performed the largest transcriptome-wide association study (TWAS) for PPD (482 cases, 859 controls) to date using RNA-sequencing in whole blood and deconvoluted cell types. No transcriptional changes were observed in whole blood. B-cells showed a majority of transcriptome-wide significant results (891 transcripts representing 789 genes) with pathway analyses implicating altered B-cell activation and insulin resistance. Integration of other data types revealed cell type-specific DNA methylation loci and disease-associated eQTLs (deQTLs), but not hormones/neuropeptides (estradiol, progesterone, oxytocin, BDNF), serve as regulators for part of the transcriptional differences between cases and controls. Further, deQTLs were enriched for several brain region-specific eQTLs, but no overlap with MDD risk loci was observed. Altogether, our results constitute a convergence of evidence for pathways most affected in PPD with data across different biological mechanisms.

published proceedings

  • Mol Psychiatry

altmetric score

  • 219.13

author list (cited authors)

  • Guintivano, J., Aberg, K. A., Clark, S. L., Rubinow, D. R., Sullivan, P. F., Meltzer-Brody, S., & van den Oord, E.

citation count

  • 2

complete list of authors

  • Guintivano, Jerry||Aberg, Karolina A||Clark, Shaunna L||Rubinow, David R||Sullivan, Patrick F||Meltzer-Brody, Samantha||van den Oord, Edwin JCG

publication date

  • June 2022