{"title":"Genetic causal association between heart failure, frailty and poisoning by narcotics and psychodysleptics: A two-sample Mendelian randomization.","authors":"Bing Wang, Hong Yu, Meng Cai, Xianqiao Xie","doi":"10.1002/bcp.70091","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Observational studies have suggested associations between heart failure (HF), frailty and poisoning by narcotics and psychodysleptics (PNP). However, establishing causal relationships has been challenging. This study used a two-sample Mendelian randomization (MR) approach to investigate the genetically proxied causality between HF, frailty and PNP.</p><p><strong>Methods: </strong>Summary-level data from genome-wide association studies (GWAS) were utilized to investigate the causal relationship between frailty index (FI) and PNP risk, PNP and HF risk, as well as the bidirectional relationship between FI and HF. Various MR methods, including inverse-variance weighted (IVW), MR-Egger, weighted median and weighted mode, were employed. Horizontal pleiotropy, heterogeneities and the robustness of genetic variants were assessed using MR-Egger intercept tests, Cochran's Q test and leave-one-out analyses. The MR-PRESSO outlier test was applied to identify and remove outlier variants to mitigate potential pleiotropy.</p><p><strong>Results: </strong>Significant genetic causal associations were observed between FI and HF (IVW: OR = 1.42, 95% CI: 1.16-1.74) and between HF and FI (IVW: OR = 1.09, 95% CI: 1.05-1.14). However, no causal relationships were found between other variables. Sensitivity analyses demonstrated no evidence of horizontal pleiotropy or heterogeneity, confirming the robustness of the results.</p><p><strong>Conclusions: </strong>This MR study provides genetic evidence of a bidirectional causal relationship between FI and HF, highlighting the intertwined nature of frailty and heart failure. No genetically proxied causal associations were observed between FI and PNP or between PNP and HF. Further research, including age-stratified and longitudinal studies, is needed to validate these findings and explore the underlying mechanisms.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"British journal of clinical pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/bcp.70091","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Aims: Observational studies have suggested associations between heart failure (HF), frailty and poisoning by narcotics and psychodysleptics (PNP). However, establishing causal relationships has been challenging. This study used a two-sample Mendelian randomization (MR) approach to investigate the genetically proxied causality between HF, frailty and PNP.
Methods: Summary-level data from genome-wide association studies (GWAS) were utilized to investigate the causal relationship between frailty index (FI) and PNP risk, PNP and HF risk, as well as the bidirectional relationship between FI and HF. Various MR methods, including inverse-variance weighted (IVW), MR-Egger, weighted median and weighted mode, were employed. Horizontal pleiotropy, heterogeneities and the robustness of genetic variants were assessed using MR-Egger intercept tests, Cochran's Q test and leave-one-out analyses. The MR-PRESSO outlier test was applied to identify and remove outlier variants to mitigate potential pleiotropy.
Results: Significant genetic causal associations were observed between FI and HF (IVW: OR = 1.42, 95% CI: 1.16-1.74) and between HF and FI (IVW: OR = 1.09, 95% CI: 1.05-1.14). However, no causal relationships were found between other variables. Sensitivity analyses demonstrated no evidence of horizontal pleiotropy or heterogeneity, confirming the robustness of the results.
Conclusions: This MR study provides genetic evidence of a bidirectional causal relationship between FI and HF, highlighting the intertwined nature of frailty and heart failure. No genetically proxied causal associations were observed between FI and PNP or between PNP and HF. Further research, including age-stratified and longitudinal studies, is needed to validate these findings and explore the underlying mechanisms.
期刊介绍:
Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.