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

Haoxin Peng; Xiangrong Wu; Fan Ge; Zhenyu Huo; Yaokai Wen; Caichen Li; Jinsheng Lin; Hengrui Liang; Ran Zhong; Jun Liu; Runchen Wang; Jianxing He; Wenhua Liang

doi:10.21037/atm-20-5372

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

Ann Transl Med. 2021 Mar;9(5):401. doi: 10.21037/atm-20-5372.

Authors

Haoxin Peng^{1

2}, Xiangrong Wu^{1

2}, Fan Ge^{1

3}, Zhenyu Huo^{1

2}, Yaokai Wen^{1

2}, Caichen Li¹, Jinsheng Lin^{1

2}, Hengrui Liang¹, Ran Zhong¹, Jun Liu¹, Runchen Wang^{1

2}, Jianxing He¹, Wenhua Liang¹

Affiliations

¹ Department of Thoracic Oncology and Surgery, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
² Nanshan School, Guangzhou Medical University, Guangzhou, China.
³ First Clinical School, Guangzhou Medical University, Guangzhou, China.

Abstract

Background: Epidemiologic findings suggested that bipolar disorder (BD) may be associated with an increased risk of breast cancer. However, there are few studies that comprehensively evaluating their correlation and the causal effect remains unknown. With a two-sample Mendelian randomization (MR) approach, we were able to investigate the causal relationship between genetically predicted BD and breast cancer risk.

Methods: Utilizing 14 BD-related single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) identified by the latest genome-wide association studies (GWASs), we investigated the correlation between genetically predicted BD and breast cancer risk using summary statistics from the Breast Cancer Association Consortium, with a total of 122,977 cases and 105,974 controls. Study-specific estimates were summarized using inverse variance weighted (IVW) method. To further evaluate the pleiotropy, the weighted median and the MR-Egger regression method were implemented. Subgroup analyses according to different immunohistochemical types of breast cancer were also conducted.

Results: MR analyses demonstrated that genetically predicted BD was causally associated with an increased risk of breast cancer (OR =1.059; 95% CI: 1.008-1.112, P=0.0229). When results were examined by immunohistochemical type, no causal effects between genetically predicted BD and estrogen receptor (ER)-positive breast cancer (OR =1.049, 95% CI: 0.999-1.102 P=0.0556) and ER-negative breast cancer (OR =1.032, 95% CI: 0.953-1.116 P=0.4407) were observed. Additionally, the results demonstrated the absence of the horizontal pleiotropy.

Conclusions: Our findings provided evidence for a causal relationship between genetically predicted BD and an increased risk of breast cancer overall. Further studies are warranted to investigate the underlying mechanism.

Keywords: Bipolar disorder (BD); Mendelian randomization (MR); breast cancer.