Investigating the relationship between depression and breast cancer: observational and genetic analyses

• Published in: BMC medicine 2023-05, Vol.21 (1), p.170-170, Article 170
• Main Authors: Wu, Xueyao, Zhang, Wenqiang, Zhao, Xunying, Zhang, Li, Xu, Minghan, Hao, Yu, Xiao, Jinyu, Zhang, Ben, Li, Jiayuan, Kraft, Peter, Smoller, Jordan W, Jiang, Xia
• Format: Article
• Language: English
• Subjects: Biobanks; Breast cancer; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Causal inference; Chromosome 9; Cohort analysis; Consortia; Correlation analysis; Depression; Depression - epidemiology; Depression - genetics; Depression, Mental; Diagnosis; Estrogen receptors; Estrogens; Female; Genealogy; Genetic analysis; Genetic aspects; Genetic correlation; Genetic relationship; Genome-wide association studies; Genome-Wide Association Study; Genomes; Hormone replacement therapy; Humans; Longitudinal association; Medicin och hälsovetenskap; Mendelian Randomization Analysis; Mental depression; Mental disorders; Mental health; Meta-analysis; Morbidity; Observational studies; Pleiotropic loci; Polymorphism, Single Nucleotide - genetics; Psychological aspects; Receptors, Estrogen - genetics; Risk; Statistical analysis; Womens health
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-023-02876-w

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. 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). 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 ([Formula: see text] = 0.08, P = 3.00 × 10 ), consistent across ER + ([Formula: see text] = 0.06, P = 6.30 × 10 ) and ER - subtypes ([Formula: see text] = 0.08, P = 7.20 × 10 ). 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. 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.