Causal relationship between affect disorders and endometrial cancer: a Mendelian randomisation study

Abstract

Background

The aim was to assess the causal relationship between depression and anxiety disorders and endometrial cancer.

Method

We performed two-sample Mendelian randomisation analysis using summary statistics from genome-wide association studies to assess associations of major depressive disorder, anxiety and stress-related disorders with endometrial cancer. The genome-wide association studies(GWASs) data were derived from participants of predominantly European ancestry included in the Genome-wide Association Research Collaboration. Inverse variance-weighted, MR-Egger and weighted median MR analyses were performed, together with a range of sensitivity analyses.

Results

Mendelian randomisation analysis showed no statistically significant genetic responsibility effect of anxiety and stress-related disorders on any pathological type of endometrial cancer. Only the effect of major depressive disorder under the inverse variance weighting method increasing the risk of endometrial endometrial cancer (effect 0.004 p = 0.047) and the effect of major depressive disorder under the MR-Egger method decreasing endometrial cancer of all pathology types (effect −0.691 p = 0.015) were statistically significant. Other Mendelian randomisation analyses did not show a statistically significant effect.

Conclusion

Major depressive disorder(MDD), anxiety and stress-related disorders(ASRD) are not genetically responsible for endometrial cancer. We consider that emotional disorders may affect endometrial cancer indirectly by affecting body mass index. This study provides us with new insights to better understand the aetiology of endometrial cancer and inform prevention strategies.

PLAIN LANGUAGE SUMMARY

This study used public genomic data to analyse association between affective disorders, including depression and anxiety, and endometrial cancer. Genes treated as instrumental variables help us understand the causal link between affective disorders and endometrial cancer through bioinformatics. In addition to this, we added type 2 diabetes, body mass index, polycystic ovary syndrome, and age at menopause for multivariate Mendelian randomisation analyses with the aim of reducing confounding bias. Because we consider these factors may potentially influence the relationship between affective disorders and endometrial cancer. Ultimately we believe that the association between depression and endometrial cancer is not as strong as that of obesity, due to the genetic correlation between depression and obesity.

Keywords:

• Affect disorder
• depression
• anxiety
• risk factor
• Mendelian randomisation

Acknowledgments

We want to acknowledge the participants and investigators of the FinnGen study. We would like to thank the University of Bristol’s Department of Epidemiology for developing a handy software package for Mendelian randomisation analysis. We thank AJE.com for providing English writing editing services.

Data availability statement

The data used in this study are publicly available and both the data and the methods of acquisition have been provided in Appendix A.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.