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

BMC Medicine

Research Article

Peter Kraft¹  Wenqiang Zhang²  Xunying Zhao²  Yu Hao²  Jinyu Xiao²  Ben Zhang²  Minghan Xu²  Jiayuan Li²  Xueyao Wu²  Li Zhang²  Xia Jiang³  Jordan W. Smoller⁴ 

[1] Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA;Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA;Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16 Ren Min Nan Lu, 610041, Chengdu, Sichuan, People’s Republic of China;Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16 Ren Min Nan Lu, 610041, Chengdu, Sichuan, People’s Republic of China;Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Solna, Stockholm, Sweden;Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China;Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA;Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA;

关键词: Depression;    Breast cancer;    Longitudinal association;    Genetic correlation;    Pleiotropic loci;    Causal inference;   

DOI  :  10.1186/s12916-023-02876-w

 received in 2022-11-16, accepted in 2023-04-20,  发布年份 2023

来源: Springer

【 摘 要 】

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\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$${r}_{g}$$\end{document} = 0.08, P = 3.00 × 10–4), consistent across ER + (rg\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$${r}_{g}$$\end{document} = 0.06, P = 6.30 × 10–3) and ER − subtypes (rg\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$${r}_{g}$$\end{document} = 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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