孟德尔随机化
射血分数
全基因组关联研究
内科学
心力衰竭
遗传关联
射血分数保留的心力衰竭
生物
基因
医学
遗传学
单核苷酸多态性
遗传变异
基因型
作者
Qian Yang,Qian Yang,Xinyuan Wu,Ruizhi Zheng,Hong Lin,Shuangyuan Wang,Jacob Joseph,Yan V. Sun,Mian Li,Tiange Wang,Zhiyun Zhao,Mingqing Xu,Jieli Lu,Yuhong Chen,Guang Ning,Weiqing Wang,Yufang Bi,Jie Zheng,Yu Xu
标识
DOI:10.1016/j.xcrm.2023.101382
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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