Using Mendelian randomization provides genetic insights into potential targets for sepsis treatment

作者全名：Xia, Rui; Sun, Meng; Yin, Jing; Zhang, Xu; Li, Jianhua

作者地址：[Xia, Rui; Li, Jianhua] Chongqing Univ, Jiangjin Hosp, Dept Crit Care Med, Chongqing 402260, Peoples R China; [Sun, Meng] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Anesthesiol, Wuhan 430022, Peoples R China; [Yin, Jing] Nanjing Univ, Affiliated Hosp, Nanjing Jinling Hosp, Med Sch, Nanjing 210016, Peoples R China; [Zhang, Xu] Chongqing Med Univ, Ctr Reprod Med, Women & Childrens Hosp, Chongqing 400013, Peoples R China; [Zhang, Xu] Chongqing Hlth Ctr Women & Children, Ctr Reprod Med, Chongqing 400013, Peoples R China; [Zhang, Xu] Chongqing Reprod Genet Inst, Chongqing 400013, Peoples R China

通信作者：Li, JH (通讯作者)，Chongqing Univ, Jiangjin Hosp, Dept Crit Care Med, Chongqing 402260, Peoples R China.; Zhang, X (通讯作者)，Chongqing Med Univ, Ctr Reprod Med, Women & Childrens Hosp, Chongqing 400013, Peoples R China.; Zhang, X (通讯作者)，Chongqing Hlth Ctr Women & Children, Ctr Reprod Med, Chongqing 400013, Peoples R China.; Zhang, X (通讯作者)，Chongqing Reprod Genet Inst, Chongqing 400013, Peoples R China.

来源：SCIENTIFIC REPORTS

ESI学科分类：Multidisciplinary

WOS号：WOS:001201413300025

JCR分区：Q1

影响因子：3.8

年份：2024

卷号：14

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Mendelian randomization; Sepsis; Drug target prediction

摘要：Sepsis is recognized as a major contributor to the global disease burden, but there is a lack of specific and effective therapeutic agents. Utilizing Mendelian randomization (MR) methods alongside evidence of causal genetics presents a chance to discover novel targets for therapeutic intervention. MR approach was employed to investigate potential drug targets for sepsis. Pooled statistics from IEU-B-4980 comprising 11,643 cases and 474,841 controls were initially utilized, and the findings were subsequently replicated in the IEU-B-69 (10,154 cases and 454,764 controls). Causal associations were then validated through colocalization. Furthermore, a range of sensitivity analyses, including MR-Egger intercept tests and Cochran's Q tests, were conducted to evaluate the outcomes of the MR analyses. Three drug targets (PSMA4, IFNAR2, and LY9) exhibited noteworthy MR outcomes in two separate datasets. Notably, PSMA4 demonstrated not only an elevated susceptibility to sepsis (OR 1.32, 95% CI 1.20-1.45, p = 1.66E-08) but also exhibited a robust colocalization with sepsis (PPH4 = 0.74). According to the present MR analysis, PSMA4 emerges as a highly encouraging pharmaceutical target for addressing sepsis. Suppression of PSMA4 could potentially decrease the likelihood of sepsis.

基金机构：Joint project of Chongqing Health Commision and Science and Technology Bureau [2024MSXM082]

基金资助正文：This study was funded by Joint project of Chongqing Health Commision and Science and Technology Bureau (2024MSXM082).