In:
BMC Medicine, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2023-05-04)
Abstract:
Both 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. Methods We 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). Results Observational 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 ( $${r}_{g}$$ r g = 0.08, P = 3.00 × 10 –4 ), consistent across ER + ( $${r}_{g}$$ r g = 0.06, P = 6.30 × 10 –3 ) and ER − subtypes ( $${r}_{g}$$ 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. Conclusions Our 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.
Type of Medium:
Online Resource
ISSN:
1741-7015
DOI:
10.1186/s12916-023-02876-w
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
2131669-7
