Nature Communications (Oct 2024)
Transcriptome-wide Mendelian randomization during CD4+ T cell activation reveals immune-related drug targets for cardiometabolic diseases
- Xueyan Wu,
- Hui Ying,
- Qianqian Yang,
- Qian Yang,
- Haoyu Liu,
- Yilan Ding,
- Huiling Zhao,
- Zhihe Chen,
- Ruizhi Zheng,
- Hong Lin,
- Shuangyuan Wang,
- Mian Li,
- Tiange Wang,
- Zhiyun Zhao,
- Min Xu,
- Yuhong Chen,
- Yu Xu,
- Emma E. Vincent,
- Maria Carolina Borges,
- Tom R. Gaunt,
- Guang Ning,
- Weiqing Wang,
- Yufang Bi,
- Jie Zheng,
- Jieli Lu
Affiliations
- Xueyan Wu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Hui Ying
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Qianqian Yang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Qian Yang
- MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol
- Haoyu Liu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Yilan Ding
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Huiling Zhao
- MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol
- Zhihe Chen
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Ruizhi Zheng
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Hong Lin
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Shuangyuan Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Mian Li
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Tiange Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Zhiyun Zhao
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Min Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Yuhong Chen
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Yu Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Emma E. Vincent
- MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol
- Maria Carolina Borges
- MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol
- Tom R. Gaunt
- MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol
- Guang Ning
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Weiqing Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Yufang Bi
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Jie Zheng
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- Jieli Lu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- DOI
- https://doi.org/10.1038/s41467-024-53621-7
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 16
Abstract
Abstract Immunity has shown potentials in informing drug development for cardiometabolic diseases, such as type 2 diabetes (T2D) and coronary artery disease (CAD). Here, we performed a transcriptome-wide Mendelian randomization (MR) study to estimate the putative causal effects of 11,021 gene expression profiles during CD4+ T cells activation on the development of T2D and CAD. Robust MR and colocalization evidence was observed for 162 genes altering T2D risk and 80 genes altering CAD risk, with 12% and 16% respectively demonstrating CD4+ T cell specificity. We observed temporal causal patterns during T cell activation in 69 gene-T2D pairs and 34 gene-CAD pairs. These genes were eight times more likely to show robust genetic evidence. We further identified 25 genes that were targets for drugs under clinical investigation, including LIPA and GCK. This study provides evidence to support immune-to-metabolic disease connections, and prioritises immune-mediated drug targets for cardiometabolic diseases.
