| Title: | Investigating the relationship between depression and breast cancer: observational and genetic analyses |
| Journal: | BMC Medicine |
| Published: | 4 May 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37143087/ |
| DOI: | https://doi.org/10.1186/s12916-023-02876-w |
| URL: | https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02876-w |
Publication 11410
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Abstract
BackgroundBoth depression and breast cancer (BC) contribute to a substantial global burden of morbidity and mortality among women, and previous studies have observed a potential depression-BC link. We aimed to comprehensively characterize the phenotypic and genetic relationships between depression and BC.MethodsWe first evaluated phenotypic association using longitudinal follow-up data from the UK Biobank (N = 250,294). We then investigated genetic relationships leveraging summary statistics from the hitherto largest genome-wide association study of European individuals conducted for depression (N = 500,199), BC (N = 247,173), and its subtypes based on the status of estrogen receptor (ER + : N = 175,475; ER − : N = 127,442).ResultsObservational analysis suggested an increased hazard of BC in depression patients (HR = 1.10, 95%CIs = 0.95-1.26). A positive genetic correlation between depression and overall BC was observed (rg$${r}_{g}$$ = 0.08, P = 3.00 × 10-4), consistent across ER + (rg$${r}_{g}$$ = 0.06, P = 6.30 × 10-3) and ER − subtypes (rg$${r}_{g}$$ = 0.08, P = 7.20 × 10-3). Several specific genomic regions showed evidence of local genetic correlation, including one locus at 9q31.2, and four loci at, or close, to 6p22.1. Cross-trait meta-analysis identified 17 pleiotropic loci shared between depression and BC. TWAS analysis revealed five shared genes. Bi-directional Mendelian randomization suggested risk of depression was causally associated with risk of overall BC (OR = 1.12, 95%Cis = 1.04-1.19), but risk of BC was not causally associated with risk of depression.ConclusionsOur work demonstrates a shared genetic basis, pleiotropic loci, and a putative causal relationship between depression and BC, highlighting a biological link underlying the observed phenotypic relationship; these findings may provide important implications for future studies aimed reducing BC risk.</p>
12 Authors
- Xueyao Wu
- Wenqiang Zhang
- Xunying Zhao
- Li Zhang
- Minghan Xu
- Yu Hao
- Jinyu Xiao
- Ben Zhang
- Jiayuan Li
- Peter Kraft
- Jordan W. Smoller
- Xia Jiang
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