Transcriptome-wide association study for postpartum depression implicates altered B-cell activation and insulin resistance.
Mol Psychiatry
; 27(6): 2858-2867, 2022 06.
Article
em En
| MEDLINE
| ID: mdl-35365803
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Depressão Pós-Parto
/
Estudo de Associação Genômica Ampla
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article