Sex-stratified genome-wide association and transcriptome-wide Mendelian randomization studies reveal drug targets of heart failure

被引：4
|
作者：
Yang, Qianqian [1 ,2 ]
Yang, Qian [3 ]
Wu, Xueyan [1 ,2 ]
Zheng, Ruizhi [1 ,2 ]
Lin, Hong [1 ,2 ]
Wang, Shuangyuan [1 ,2 ]
Joseph, Jacob [4 ,5 ]
Sun, Yan V. [6 ,7 ]
Li, Mian [1 ,2 ]
Wang, Tiange [1 ,2 ]
Zhao, Zhiyun [1 ,2 ]
Xu, Min [1 ,2 ]
Lu, Jieli [1 ,2 ]
Chen, Yuhong [1 ,2 ]
Ning, Guang [1 ,2 ]
Wang, Weiqing [1 ,2 ]
Bi, Yufang [1 ,2 ]
Zheng, Jie [1 ,2 ]
Xu, Yu [1 ,2 ]
机构：
[1] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Endocrine & Metab Dis, Dept Endocrine & Metab Dis,Sch Med, Shanghai, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Natl Clin Res Ctr Metab Dis, Shanghai Natl Ctr Translat Med, Ruijin Hosp,Sch Med,Key Lab Endocrine & Metab Dis,, Shanghai, Peoples R China
[3] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, England
[4] VA Providence Healthcare Syst, Cardiol Sect, 830 Chalkstone Ave, Providence, RI 02908 USA
[5] Brown Univ, Dept Med, Warren Alpert Med Sch, 222 Richmond St, Providence, RI 02903 USA
[6] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA USA
[7] Atlanta VA Hlth Care Syst, Decatur, GA USA
来源：
CELL REPORTS MEDICINE | 2024年 / 5卷 / 02期
基金：
中国国家自然科学基金; 英国惠康基金; 英国医学研究理事会;
关键词：
NATRIURETIC PEPTIDE RECEPTOR; GENETIC-VARIANTS; SERINE HYDROXYMETHYLTRANSFERASE; RISK; DISEASE; EPIDEMIOLOGY; INHIBITION; AGENT; SORT1;
D O I：
10.1016/j.xcrm.2023.101382
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
The prevalence of heart failure (HF) subtypes, which are classified by left ventricular ejection fraction (LVEF), demonstrate significant sex differences. Here, we perform sex -stratified genome-wide association studies (GWASs) on LVEF and transcriptome-wide Mendelian randomization (MR) on LVEF, all -cause HF, HF with reduced ejection fraction (HFrEF), and HF with preserved ejection fraction (HFpEF). The sex -stratified GWASs of LVEF identified three sex -specific loci that were exclusively detected in the sex -stratified GWASs. Three drug target genes show sex -differential effects on HF/HFrEF via influencing LVEF, with NPR2 as the target gene for the HF drug Cenderitide under phase 2 clinical trial. Our study highlights the importance of considering sex -differential genetic effects in sex -balanced diseases such as HF and emphasizes the value of sex -stratified GWASs and MR in identifying putative genetic variants, causal genes, and candidate drug targets for HF, which is not identifiable using a sex -combined strategy.
引用
收藏
页数：19
相关论文
共 50 条
  • [41] Identification of novel targets for ankylosing spondylitis through integrated transcriptome-wide association analysis and Mendelian randomization: Medical thermography analysis
    Wu, Zhoutong
    Lin, Zehong
    Zhou, Honghai
    Wu, Zhouhan
    THERMAL SCIENCE AND ENGINEERING PROGRESS, 2024, 56
  • [42] Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study
    Orlova, Ekaterina
    Dudding, Tom
    Chernus, Jonathan M.
    Alotaibi, Rasha N.
    Haworth, Simon
    Crout, Richard J.
    Lee, Myoung Keun
    Mukhopadhyay, Nandita
    Feingold, Eleanor
    Levy, Steven M.
    McNeil, Daniel W.
    Foxman, Betsy
    Weyant, Robert J.
    Timpson, Nicholas J.
    Marazita, Mary L.
    Shaffer, John R.
    GENES, 2023, 14 (01)
  • [43] Integrating genome-wide methylation and transcriptome-wide analyses to reveal the genetic mechanism of milk traits in Kazakh horses
    Liu, Lingling
    Zhang, Yunting
    Ma, Haiyu
    Cao, Hang
    Liu, Wujun
    GENE, 2023, 856
  • [44] Systematic druggable genome-wide Mendelian randomization identifies therapeutic targets for lung cancer
    Song, Wenfu
    Li, Yingying
    Yao, Yaxuan
    Sun, Shiling
    Guan, Xutao
    Wang, Bing
    BMC CANCER, 2024, 24 (01)
  • [45] Based on systematic druggable genome-wide Mendelian randomization identifies therapeutic targets for diabetes
    Li, Hu
    Li, Wei
    Li, Dongyang
    Yuan, Lijuan
    Xu, Yucheng
    Su, Pengtao
    Wu, Liqiang
    Zhang, Zhiqiang
    FRONTIERS IN ENDOCRINOLOGY, 2024, 15
  • [46] Comprehensive Druggable Genome-Wide Mendelian Randomization Reveals Therapeutic Targets for Kidney Diseases
    Su Zhihang
    Xue Rui
    Wan Qijun
    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2024, 35 (10):
  • [47] Systematic druggable genome-wide Mendelian randomization identifies therapeutic targets for hyperemesis gravidarum
    Wang, Fengyang
    Ruan, Wenpeng
    Yin, Qiuyuan
    Zhu, Lei
    BMC PREGNANCY AND CHILDBIRTH, 2024, 24 (01)
  • [48] Integrating genome-wide association studies and transcriptomics prioritizes drug targets for meningioma
    Liao, Wan-Zhe
    Wang, Jia-He
    Zhong, Hua-Jie
    Wen, Shen-Yu
    Chen, Yang
    Chen, Jia-Qi
    Zhang, Xue-Kun
    Wu, Xin-Yi
    Tan, Jia-Nuo
    Li, Kun-Yi
    Mo, Shao-Cong
    Wang, Li-Jun
    BRAIN COMMUNICATIONS, 2025, 7 (02)
  • [49] Identifying therapeutic targets for ovarian cancer: a druggable genome-wide Mendelian randomization study
    Chen, Siyu
    Zheng, Min
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2024, 34 (SUPPL_3) : A206 - A206
  • [50] Identifying potential drug targets for seborrheic keratosis through druggable genome-wide Mendelian randomization and colocalization analysis
    Lin, Zhipeng
    Sun, Hongyong
    Zhao, Zeng
    Wang, Aoxue
    ARCHIVES OF DERMATOLOGICAL RESEARCH, 2025, 317 (01)
12345