| Title: | Microglial function interacts with the environment to affect sex-specific depression risk |
| Journal: | Brain Behavior and Immunity |
| Published: | 25 Apr 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38670238/ |
| DOI: | https://doi.org/10.1016/j.bbi.2024.04.030 |
Publication 9845
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Abstract
There is a two-fold higher incidence of depression in females compared to men with recent studies suggesting a role for microglia in conferring this sex-dependent depression risk. In this study we investigated the nature of this relation. Using GWAS enrichment, gene-set enrichment analysis and Mendelian randomization, we found minimal evidence for a direct relation between genes functionally related to microglia and sex-dependent genetic risk for depression. We then used expression quantitative trait loci and single nucleus RNA-sequencing resources to generate polygenic scores (PGS) representative of individual variation in microglial function in the adult (UK Biobank; N = 54753-72682) and fetal (ALSPAC; N = 1452) periods. The adult microglial PGS moderated the association between BMI (UK Biobank; beta = 0.001, 95 %CI 0.0009 to 0.003, P = 7.74E-6) and financial insecurity (UK Biobank; beta = 0.001, 95 %CI 0.005 to 0.015, P = 2E-4) with depressive symptoms in females. The fetal microglia PGS moderated the association between maternal prenatal depressive symptoms and offspring depressive symptoms at 24 years in females (ALSPAC; beta = 0.04, 95 %CI 0.004 to 0.07, P = 0.03). We found no evidence for an interaction between the microglial PGS and depression risk factors in males. Our results illustrate a role for microglial function in the conferral of sex-dependent depression risk following exposure to a depression risk factor.</p>
8 Authors
- Eamon Fitzgerald
- Irina Pokhvisneva
- Sachin Patel
- Shi Yu Chan
- Ai Peng Tan
- Helen Chen
- Patricia Pelufo Silveira
- Michael J Meaney
1 Application
| Application ID | Title |
|---|---|
| 41975 | Gene Network by environment (GnxE) study of impulsivity- methodology to extend GxE studies. |
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