| Title: | Epidemiological and Genetic Analyses of Schizophrenia and Breast Cancer |
| Journal: | Schizophrenia Bulletin |
| Published: | 19 Jul 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37467357/ |
| DOI: | https://doi.org/10.1093/schbul/sbad106 |
Publication 11638
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Abstract
BACKGROUND AND HYPOTHESIS: While the phenotypic association between schizophrenia and breast cancer has been observed, the underlying intrinsic link is not adequately understood. We aim to conduct a comprehensive interrogation on both phenotypic and genetic relationships between schizophrenia and breast cancer.</p>
STUDY DESIGN: We first used data from UK Biobank to evaluate a phenotypic association and performed an updated meta-analysis incorporating existing cohort studies. We then leveraged genomic data to explore the shared genetic architecture through a genome-wide cross-trait design.</p>
STUDY RESULTS: Incorporating results of our observational analysis, meta-analysis of cohort studies suggested a significantly increased incidence of breast cancer among women with schizophrenia (RR = 1.30, 95% CIs = 1.14-1.48). A positive genomic correlation between schizophrenia and overall breast cancer was observed (rg = 0.12, P = 1.80 × 10-10), consistent across ER+ (rg = 0.10, P = 5.74 × 10-7) and ER- subtypes (rg = 0.09, P = .003). This was further corroborated by four local signals. Cross-trait meta-analysis identified 23 pleiotropic loci between schizophrenia and breast cancer, including five novel loci. Gene-based analysis revealed 27 shared genes. Mendelian randomization demonstrated a significantly increased risk of overall breast cancer (OR = 1.07, P = 4.81 × 10-10) for genetically predisposed schizophrenia, which remained robust in subgroup analysis (ER+: OR = 1.10, P = 7.26 × 10-12; ER-: OR = 1.08, P = 3.50 × 10-6). No mediation effect and reverse causality was found.</p>
CONCLUSIONS: Our study demonstrates an intrinsic link underlying schizophrenia and breast cancer, which may inform tailored screening and management of breast cancer in schizophrenia.</p>
19 Authors
- Mingshuang Tang
- Xueyao Wu
- Wenqiang Zhang
- Huijie Cui
- Li Zhang
- Peijing Yan
- Chao Yang
- Yutong Wang
- Lin Chen
- Chenghan Xiao
- Yunjie Liu
- Yanqiu Zou
- Chunxia Yang
- Ling Zhang
- Yuqin Yao
- Zhenmi Liu
- Jiayuan Li
- Xia Jiang
- Ben Zhang
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