COVID-19 and stroke MR study: data errors, timing gaps, statistical flaws

TL;DR

This paper points out major flaws in a study claiming a causal link between COVID-19 and stroke, including data misattribution, timing issues, and lack of statistical corrections.

Contribution

The paper identifies critical methodological flaws in a Mendelian randomization study on COVID-19 and stroke.

Findings

The eQTL data were incorrectly attributed to GTEx instead of the eQTLGen Consortium.

Outcome data predate the pandemic, violating assumptions of causal inference.

Lack of multiple testing correction increases false positive risk in gene pathway analysis.

Abstract

This correspondence critiques the Mendelian randomization study by Zhang et al. on the causal link between COVID-19 and ischemic stroke, highlighting three methodological concerns. First, the study incorrectly attributes the eQTL data to the GTEx database, whereas the actual source is the eQTLGen Consortium, necessitating correction for accurate data provenance. Second, the outcome data (collected prior to 2018) predate the COVID-19 pandemic (post-2019), violating the relevance assumption in instrumental variable analysis. This temporal mismatch may render observed associations biologically implausible, reflecting genetic pleiotropy or residual confounding rather than causal effects of SARS-CoV-2 infection. Third, the absence of multiple testing correction elevates the risk of false positives, undermining the validity of subsequent gene pathway analyses. Addressing these issues—revising data attribution, clarifying temporal limitations, and enhancing statistical rigor—would strengthen the study’s reliability and translational implications.