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：

英国惠康基金; 英国医学研究理事会; 中国国家自然科学基金;

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.

引用

页数：19

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