| Title: | Association of Hypnotic Drug Use and Infectious Disease: Observational Associations and Target-Specific Genetic Evidence |
| Journal: | Current Neuropharmacology |
| Published: | 12 Aug 2026 |
| DOI: | https://doi.org/10.2174/011570159x481446260730094320 |
Publication 21159
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Abstract
Introduction: Observational studies suggest associations between hypnotic use and increased infection risk, but causality remains unclear. This relationship was investigated using prospective cohort analysis and drug-target Mendelian randomization (MR). Methods: Approximately 453,826 UK Biobank participants of white British descent, including 2,290 regular hypnotic users were analyzed. Cox models estimated associations between hypnotic use and five infectious outcomes: influenza, pneumonia, urinary tract infection, intestinal infection, and sepsis. Drug-target MR explored the causal effects of hypnotic-related target genes on infection risk using cis-eQTLs from blood and brain tissues, complemented by tissue-specific MR and colocalization analyses. results: During a median 15.5-year follow-up, hypnotic use was associated with increased risks of all five infectious outcomes (all P < 0.01). Drug-target MR identified BRD2 as potentially causally associated with intestinal infection (OR 1.049; 95% CI 1.032-1.066; FDR < 0.001), with strong colocalization in frontal cortex (PPH4 = 0.997). Other hypnotic gene targets were associated with both increased and decreased risks for various infectious outcomes. Results: During a median 15.5-year follow-up, hypnotic use was associated with increased risks of all five infectious outcomes (P < 0.01). Drug-target MR identified a potential causal association between BRD2 and intestinal infection (OR 1.049; 95% CI 1.032-1.066; FDR < 0.001), with strong colocalization (PPH4 = 0.997 in BrainMeta and 0.933 in GTEx frontal cortex). However, associations with infection risk for other evaluated targets varied in direction. Discussion: The lack of consistent genetic support for other targets suggests broad observational associations may partly reflect confounding or indirect effects, rather than uniform causal mechanisms. BRD2 may influence intestinal infection through central neuroimmune regulatory mechanisms. However, constraints in brain tissue data mean these genetic findings should be interpreted as exploratory. Conclusions: Regular hypnotic use was associated with multiple infections in observational analyses, but drug-target MR identified a potential association only for BRD2. This divergence underscores the need for experimental validation to better account for confounding by indication, detection bias, and unmeasured insomnia severity </p>
11 Authors
- Wanting Huang
- Wei Guo
- Jiazhen Zheng
- Huiying Zhang
- Zhihao Guo
- Hui Xia
- Hui Yan
- Yuqing Li
- Jihui Zhang
- Sizhi Ai
- Dewei Shang
1 Application
| Application ID | Title |
|---|---|
| 93604 | Life-course risk and protective factors associated with complex diseases |
Enabling scientific discoveries that improve human health