Genetically predicted bipolar disorder is causally associated with an increased risk of breast cancer: a two-sample Mendelian randomization analysis

Peng, Haitao; Xiao-yue, WU; Ge, Fan; Huo, Zhenyu; Wen, Yujie; Li, Caichen; Lin, Jinsheng; Liang, Hengrui; Zhong, Ran; Li, Jun; Wang, Runchen; He, Jianxing; Liang, Wenhua

doi:10.21037/atm-20-5372

Cited by 6 publications

(5 citation statements)

References 49 publications

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“…The causality of BD and BC risk is controversial [41,42]. In our MR research, BD failed to be linked to BC incidence, and our results differ from the published studies [43]. Although more IVs for exposure-related SNPs were used in this article, the IVs used for exposure-related in this article included Asian populations [43].…”

Section: Discussioncontrasting

confidence: 73%

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Severe mental illness and the risk of breast cancer: A two-sample, two-step multivariable Mendelian randomization study

Cui,

Lu,

Shao

et al. 2023

PLoS ONE

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Background Based on epidemiological reports, severe mental illness (SMI) and breast cancer (BC) risk are linked positively. However, it is susceptible to clinical confounding factors, such as smoking, alcohol consumption, etc. Here, we performed a two-sample, two-step multivariable Mendelian randomization (MR) research to explore how the SMI etiologically influences BC risk and to quantify mediating effects of known modifiable risk factors. Methods Data concerning the single nucleotide polymorphism (SNP)-associated with schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), and BC were obtained from two large consortia: the Breast Cancer Association Consortium (BCAC) and the Psychiatric Genomics Consortium (PGC). Then, the correlations of the previous SMI with the BC prevalence and the potential impact of mediators were explored through the two-sample and two-step MR analyses. Results In two-sample MR, schizophrenia increased BC incidence (odds ratio (OR) 1.06, 95% confidence interval (CI) 1.02–1.10, P = 0.001). In subgroup analysis, schizophrenia increased ER+ BC (OR 1.06, 95% CI 1.03–1.10, P = 0.0009) and ER-BC (OR 1.06, 95% CI 1.01–1.11, P = 0.0123) incidences. Neither MDD nor BD elevated the BC risk. In two-step MR, smoking explained 11.29% of the schizophrenia-all BC risk association. Conclusions Our study indicates that schizophrenia increases susceptibility to breast cancer, with smoking playing a certain mediating role. Therefore, BC screening and smoking should be incorporated into the health management of individuals with schizophrenia.

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Section: Discussioncontrasting

confidence: 73%

“…Although more IVs for exposure-related SNPs were used in this article, the IVs used for exposure-related in this article included Asian populations [43]. In contrast, the outcome-related IVs were from the European populations, leading to errors in the results [43].…”

Section: Discussionmentioning

confidence: 99%

Severe mental illness and the risk of breast cancer: A two-sample, two-step multivariable Mendelian randomization study

Cui,

Lu,

Shao

et al. 2023

PLoS ONE

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“…It was noted in 2022 that a number of breast cancer patients exhibited symptoms similar to those of post-traumatic stress disorder, which were thought to be mediated by chronic inflammation, such as NF-κB, AKt, p53, and other inflammatory pathways ( 70 ). Another MR analysis indicated that bipolar disorder was causally linked to a higher breast cancer rate ( 71 ). On the one hand, the reason why our conclusion differed from previous ones might be that the sample size of GWAS data was not large enough to produce statistical differences, on the other hand, previous results might be affected by a variety of biases or confounding factors.…”

Section: Discussionmentioning

confidence: 99%

An exploration of the correlations between seven psychiatric disorders and the risks of breast cancer, breast benign tumors and breast inflammatory diseases: Mendelian randomization analyses

et al. 2023

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BackgroundPrevious observational studies have showed that certain psychiatric disorders may be linked to breast cancer risk, there is, however, little understanding of relationships between mental disorders and a variety of breast diseases. This study aims to investigate if mental disorders influence the risks of overall breast cancer, the two subtypes of breast cancer (ER+ and ER-), breast benign tumors and breast inflammatory diseases.MethodsDuring our research, genome-wide association study (GWAS) data for seven psychiatric disorders (schizophrenia, major depressive disorder, bipolar disorder, post-traumatic stress disorder, panic disorder, obsessive-compulsive disorder and anorexia nervosa) from the Psychiatric Genomics Consortium (PGC) and the UK Biobank were selected, and single-nucleotide polymorphisms (SNPs) significantly linked to these mental disorders were identified as instrumental variables. GWAS data for breast diseases came from the Breast Cancer Association Consortium (BCAC) as well as the FinnGen consortium. We performed two-sample Mendelian randomization (MR) analyses and multivariable MR analyses to assess these SNPs’ effects on various breast diseases. Both heterogeneity and pleiotropy were evaluated by sensitivity analyses.ResultsWhen the GWAS data of psychiatric disorders were derived from the PGC, our research found that schizophrenia significantly increased the risks of overall breast cancer (two-sample MR: OR 1.05, 95%CI [1.03-1.07], p = 3.84 × 10−6; multivariable MR: OR 1.06, 95%CI [1.04-1.09], p = 2.34 × 10−6), ER+ (OR 1.05, 95%CI [1.02-1.07], p = 5.94 × 10−5) and ER- (two-sample MR: OR 1.04, 95%CI [1.01-1.07], p = 0.006; multivariable MR: OR 1.06, 95%CI [1.02-1.10], p = 0.001) breast cancer. Nevertheless, major depressive disorder only showed significant positive association with overall breast cancer (OR 1.12, 95%CI [1.04-1.20], p = 0.003) according to the two-sample MR analysis, but not in the multivariable MR analysis. In regards to the remainder of the mental illnesses and breast diseases, there were no significant correlations. While as for the data from the UK Biobank, schizophrenia did not significantly increase the risk of breast cancer.ConclusionsThe correlation between schizophrenia and breast cancer found in this study may be false positive results caused by underlying horizontal pleiotropy, rather than a true cause-and-effect relationship. More prospective studies are still needed to be carried out to determine the definitive links between mental illnesses and breast diseases.

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“…Individuals with bipolar disorder and their unaffected siblings under 50 years of age had a higher chance of developing breast cancer than those in the control group. The correlation between bipolar disorder and the younger population’s susceptibility to bipolar disorder and higher cancer risk could indicate a genetic overlap in the pathophysiology of neurodevelopment ( McGinty et al, 2012 ; Peng et al, 2021 ; Chen et al, 2022 ). When comorbid intellectual disability and/or birth defects are present, those with autism spectrum disorders are more likely than those without autism spectrum disorders to have cancer in their early years.…”

Section: Introduction: Background and Premisementioning

confidence: 99%

Review: Cancer and neurodevelopmental disorders: multi-scale reasoning and computational guide

Nussinov,

Yavuz,

Demirel

et al. 2024

Front. Cell Dev. Biol.

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The connection and causality between cancer and neurodevelopmental disorders have been puzzling. How can the same cellular pathways, proteins, and mutations lead to pathologies with vastly different clinical presentations? And why do individuals with neurodevelopmental disorders, such as autism and schizophrenia, face higher chances of cancer emerging throughout their lifetime? Our broad review emphasizes the multi-scale aspect of this type of reasoning. As these examples demonstrate, rather than focusing on a specific organ system or disease, we aim at the new understanding that can be gained. Within this framework, our review calls attention to computational strategies which can be powerful in discovering connections, causalities, predicting clinical outcomes, and are vital for drug discovery. Thus, rather than centering on the clinical features, we draw on the rapidly increasing data on the molecular level, including mutations, isoforms, three-dimensional structures, and expression levels of the respective disease-associated genes. Their integrated analysis, together with chromatin states, can delineate how, despite being connected, neurodevelopmental disorders and cancer differ, and how the same mutations can lead to different clinical symptoms. Here, we seek to uncover the emerging connection between cancer, including pediatric tumors, and neurodevelopmental disorders, and the tantalizing questions that this connection raises.

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Genetically predicted bipolar disorder is causally associated with an increased risk of breast cancer: a two-sample Mendelian randomization analysis

Cited by 6 publications

References 49 publications

Severe mental illness and the risk of breast cancer: A two-sample, two-step multivariable Mendelian randomization study

Severe mental illness and the risk of breast cancer: A two-sample, two-step multivariable Mendelian randomization study

An exploration of the correlations between seven psychiatric disorders and the risks of breast cancer, breast benign tumors and breast inflammatory diseases: Mendelian randomization analyses

Review: Cancer and neurodevelopmental disorders: multi-scale reasoning and computational guide

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