Evidence map›Paper›PMID 42521903›Full record

ArticleNeurocritical care2026

Mendelian Randomization Analysis of the IL-1 Cytokine Family Proteins Identifies IL1RL1 as a Potential Causal Contributor to Traumatic Brain Injury Prognosis.

Youngjune Bhak, Adel Helmy, Edward J Needham, David K Menon, Varun Warrier, Romit J Samanta, CENTER TBI Study Consortium

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Article in Neurocritical care, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Youngjune BhakDepartment of Medicine, University of Cambridge, Cambridge, UK.
Adel HelmyDepartment of Neuroscience, University of Cambridge, Cambridge, UK.
Edward J NeedhamDepartment of Neuroscience, University of Cambridge, Cambridge, UK.
David K MenonDepartment of Medicine, University of Cambridge, Cambridge, UK.
Varun WarrierDepartment of Psychiatry, University of Cambridge, Cambridge, UK.
Romit J SamantaDepartment of Medicine, University of Cambridge, Cambridge, UK. rs307@cam.ac.uk.ORCID http://orcid.org/0000-0003-0828-3183
CENTER TBI Study Consortium

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTraumatic brain injury (TBI) is a leading preventable cause of death and disability worldwide. Inflammatory mechanisms contribute to secondary brain injury, and the interleukin-1 (IL-1) cytokine family has emerged as a potential contributor. However, whether circulating IL-1-family cytokines causally influence TBI outcomes remains unknown.

methodsWe performed a two-sample Mendelian randomization (MR) analysis to evaluate the causal effects of circulating IL-1-family protein levels on TBI outcomes, using inverse-variance weighting (IVW) as the primary analytic method and publicly available genome-wide association study summary statistics.

resultsHigher genetically predicted circulating IL1RL1 (soluble ST2) levels were associated with an increased risk of unfavorable TBI outcomes (IVW β = 0.22, standard error [SE] = 0.084, P = 0.010), although we were underpowered to test the reverse direction. Sensitivity analyses demonstrated consistent effect estimates with no evidence of horizontal pleiotropy.

conclusionsThese findings provide genetic evidence that elevated circulating IL1RL1 levels are causally linked to worse TBI outcomes. This suggests the IL-33/IL1RL1 axis as a mechanistically relevant, and potentially modifiable, therapeutic target for improving recovery after TBI.

Indexed as

InterleukinsMendelian randomization analysisTraumatic brain injury

Identifiers

PMID42521903

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