Human Plasma Proteomics Links Modifiable Lifestyle Exposome to Disease Risk

medRxiv · 13 Nov 2026 · Preprint · Open access

Isaac, Ellis + 8 more

The abstract is read at the publisher; the summary is JClub's.

In >50,000 UK Biobank participants, HEAP links 169 lifestyle exposures to plasma proteomic signatures across 2,686 proteins, and proteome-based exposure scores predict disease risk.

Why it matters: Molecular readouts connecting modifiable behaviors to human disease biology are still incomplete, limiting prevention and precision medicine efforts.
What they did: The Human Exposomic Architecture of the Proteome (HEAP) integrates exposure–protein associations with disease links using mediation, Mendelian randomization, and colocalization, plus comparisons to exercise-training and glucagon-like peptide-1 receptor agonist proteomics.
The result: Only a minority of exposure-responsive proteins fit causal intermediates, while many act as biological reporters; exposure scores track behavioral change over time and predict disease risk.

AI summary of the abstract · may contain errors · not medical advice · read the paper.

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11 cites

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Human Plasma Proteomics Links Modifiable Lifestyle Exposome to Disease Risk

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Insights from epidemiology and network toxicology into the effect of volatile organic compounds exposure on thyroid function and the underlying mechanism.

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