Does COVID-19 impact the QT interval prolongation? Answers from genetic causal inference.

Publication date: Dec 10, 2024

During the COVID-19 pandemic, there has been heightened interest in the QT interval, a crucial indicator of ventricular electrical activity. Mendelian randomization (MR) is used here to investigate the genetic causation between QT interval alterations and COVID-19. Genetic proxies representing three COVID-19 phenotypes-severe, hospitalized, and COVID-19-were identified in over 1,000,000 individuals of European ancestry. Univariate two-sample Mendelian randomization (TSMR) and multi-exposure-adjusted multivariate Mendelian randomization (MVMR) were used to assess genetic causal associations between COVID-19 and QT intervals in 84,630 UK Biobank participants. The MR-robust adjusted profile score (MR-RAPS) method and radial MR frame were utilized for effect robustness and outlier variant detection, with sensitivity analyses conducted to identify horizontal pleiotropy. For every COVID-19 phenotype, univariate TSMR analysis revealed non-significant causal estimates between COVID-19 and the QT interval [COVID-19: βIVW (95% CI): -0. 44 (-1. 72, 0. 84), P = 0. 50; hospitalization: βIVW: 0. 12 (-0. 57, 0. 80), P = 0. 74; severe case: βIVW: 0. 11 (-0. 29, 0. 51), P = 0. 58]. MR-RAPS and outlier-corrected radial MR analyses further supported this null causal estimation. In confounder-adjusted MVMR analysis, this nonsignificant causality was independent of BMI, smoking, and alcohol consumption [βBMI+Alcohol+Smoking (95% CI): -0. 77 (-2. 44, 0. 91), P = 0. 37]. Sensitivity analyses did not detect any evidence of bias from horizontal pleiotropy, abnormal data distribution, or weak instruments. These findings suggest that COVID-19 does not directly causally prolong the QT interval. Inconsistent findings in observational research may be attributed to residual confounding.

Concepts Keywords
Genetic Causality
Hospitalization COVID-19
Raps Long QT Syndrome
Mendelian Randomization Analysis

Semantics

Type Source Name
disease MESH COVID-19
disease MESH causality
drug DRUGBANK Ethanol
disease MESH Long Covid
disease MESH Long QT Syndrome

Original Article

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