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

Abstract

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.

• Authors: Jerry Guintivano, Karolina A Aberg, Shaunna L Clark, David R Rubinow, Patrick F Sullivan, Samantha Meltzer-Brody, Edwin J C G van den Oord
• Journal: Molecular psychiatry (Mol Psychiatry) Vol. 27 Issue 6 Pg. 2858-2867 (06 2022) ISSN: 1476-5578 [Electronic] England
• PMID: 35365803 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Topics

• Depression, Postpartum (genetics, metabolism)
• Female
• Genome-Wide Association Study (methods)
• Humans
• Insulin Resistance (genetics)
• Transcriptome (genetics)