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; 英国医学研究理事会; 英国惠康基金;
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.
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页数：19
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