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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Breast Cancer | Research

Exploring the association between birthweight and breast cancer using summary statistics from a perspective of genetic correlation, mediation, and causality

Authors: Meng Zhang, Jiahao Qiao, Shuo Zhang, Ping Zeng

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

Background

Previous studies demonstrated a positive relationship between birthweight and breast cancer; however, inconsistent, sometimes even controversial, observations also emerged, and the nature of such relationship remains unknown.

Methods

Using summary statistics of birthweight and breast cancer, we assessed the fetal/maternal-specific genetic correlation between them via LDSC and prioritized fetal/maternal-specific pleiotropic genes through MAIUP. Relying on summary statistics we conducted Mendelian randomization (MR) to evaluate the fetal/maternal-specific origin of causal relationship between birthweight, age of menarche, age at menopause and breast cancer.

Results

With summary statistics we identified a positive genetic correlation between fetal-specific birthweight and breast cancer (rg = 0.123 and P = 0.013) as well as a negative but insignificant correlation between maternal-specific birthweight and breast cancer (rg = − 0.068, P = 0.206); and detected 84 pleiotropic genes shared by fetal-specific birthweight and breast cancer, 49 shared by maternal-specific birthweight and breast cancer. We also revealed fetal-specific birthweight indirectly influenced breast cancer risk in adulthood via the path of age of menarche or age at menopause in terms of MR-based mediation analysis.

Conclusion

This study reveals that shared genetic foundation and causal mediation commonly drive the connection between the two traits, and that fetal/maternal-specific birthweight plays substantially distinct roles in such relationship. However, our work offers little supportive evidence for the fetal origins hypothesis of breast cancer originating in utero.
Appendix
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Metadata
Title
Exploring the association between birthweight and breast cancer using summary statistics from a perspective of genetic correlation, mediation, and causality
Authors
Meng Zhang
Jiahao Qiao
Shuo Zhang
Ping Zeng
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03435-2

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