SEARCHCOHORTepidemiology, psychiatry

cohort·epidemiology, psychiatry, oncology, public health, observational study·PMC10161423

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

BMC Medicine · 12 authors, 7 centres

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This study combined a longitudinal observational analysis of 250,294 UK Biobank participants with genetic analyses using large genome-wide association study (GWAS) summary statistics.

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This study combined a longitudinal observational analysis of 250,294 UK Biobank participants with genetic analyses using large genome-wide association study (GWAS) summary statistics. The study is limited by its focus on European populations, the use of a broad depression phenotype, and the inability to fully analyze sex-specific effects due to data limitations at the time.

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cohort

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epidemiology

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ORIGINAL PAPER

PMC10161423

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

BMC Medicine

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ABSTRACT

Abstract Background 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 = 0.08, P = 3.00 × 10 –4 ), consistent across ER + ( r g = 0.06, P = 6.30 × 10 –3 ) and ER − subtypes ( 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. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-023-02876-w. Keywords: Depression, Breast cancer, Longitudinal association, Genetic correlation, Pleiotropic loci, Causal inference

CITATION EXPORT

Xueyao Wu, Wenqiang Zhang, Xunying Zhao et al.. Investigating the relationship between depression and breast cancer: observational and genetic analyses. BMC Medicine. (2023). https://doi.org/10.1186/s12916-023-02876-w

AUTHORS

12 · 7 CENTRES

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

1Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16 Ren Min Nan Lu, Chengdu, Sichuan 610041 People’s Republic of China
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA USA
3Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA USA
4Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, and Department of Psychiatry, Massachusetts General Hospital, MA Boston, USA
5Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, MA Cambridge, USA
6Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm Solna, Sweden
7Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China