Principal Investigator: Professor Ben Zhang
First Affiliated Hospital Army Medical University, Chongqing, ChinaTags: 46271, breast cancer, casual inference, gene expression, Genetic architecture, genome-wide association, phenome-wide association
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women. Genetic factors play an important role in the risk of breast cancer. Over the past decade, genome-wide association studies have identified more than 100 common susceptibility loci for breast cancer. However, these loci together account for less than 20% of the familial relative risk of breast cancer, suggesting that more loci should be identified in studies with much larger sample size. In this project, we aim to investigate the genetic architecture of breast cancer using data from the UK Biobank, our group and collaborators, as well as other public available sources. To address this issue, we will first carry out a multi-ancestry genome-wide association study of more than 700,000 subjects to identify new susceptibility loci and then do functional annotations for these variants. Second, we will conduct a phenome-wide association study to uncover the genetic architecture shared between breast cancer and other phenotypes. Finally, we will perform a mendelian randomization analysis to examine whether risk factors identified in prospective observational studies are causally associated with breast cancer. The potential causal effect of a specific exposure on the risk of breast cancer is estimated as the ratio of the coefficient of the association between genetic factor and breast cancer to that of the association between genetic factor and the exposure. We will start analyses as soon as data are available and plan to finish this project and send manuscripts to authors for review within 18 months after we receive the data. We hope that this study will facilitate our understanding of the genetic architecture of breast cancer susceptibility and may help identify new biological pathways and therapeutic targets for improving prevention and treatment of breast cancer. Our study is line with the goal of UK Biobank that dedicates to improve the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses like breast cancer.
New scope: Breast tumorigenesis is a multistage and multifactorial process, involving environmental and genetic factors as well as interactions between them. To address interactions in relation to genetic factors, we propose to extend this project and perform additional analyses to investigate gene-environment and gene-gene interactions on the risk of breast cancer using data from UK Biobank, our group and collaborators, as well as other public available sources. In addition, as UK Biobank recently released exome data for 50,000 participants and will complete the exome sequence assay on the remaining 450,000 participants by the end of 2020, we thus propose to identify rare variants associated with risk of breast cancer using these data. All these analyses are highly consistent with the study scope in the initial application and will further advance our understanding of the genetic basis of breast cancer.
Last updated Jun 10, 2019