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Published on: June 28, 2018
Plasma MERTK is causally associated with infection mortality
Michael Drozd1, Fergus Hamilton2, Chew W Cheng1
1Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK.
Background:
Infectious diseases are a major cause of mortality in spite of existing public health, anti-microbial and vaccine interventions. We aimed to define plasma proteomic associates of infection mortality and then apply Mendelian randomisation (MR) to yield biomarkers that may be causally associated.
Methods:
We used UK Biobank plasma proteomic data to associate 2923 plasma proteins with infection mortality before 31st December 2019 (240 events in 52,520 participants). Since many plasma proteins also predict non-infection mortality, we focussed on those associated with >1.5-fold risk of infection mortality in an analysis excluding survivors. Protein quantitative trait scores (pQTS) were then used to identify whether genetically predicted protein levels also associated with infection mortality. To conduct Two Sample MR, we performed a genome-wide association study (GWAS) of infection mortality using UK Biobank participants without plasma proteomic data (n = 363,953 including 984 infection deaths).
Findings:
After adjusting for clinical risk factors, 1142 plasma proteins were associated with risk of infection mortality (false discovery rate <0.05). 259 proteins were associated with >1.5-fold increased risk of infection versus non-infection mortality. Of these, we identified genetically predicted increasing MERTK concentration was associated with increased risk of infection mortality. MR supported a causal association between increasing plasma MERTK protein and infection mortality (odds ratio 1.46 per unit; 95% CI 1.15- 1.85; p = 0.002).
Conclusion:
Plasma MERTK is causally associated with infection mortality and warrants exploration as a potential therapeutic target.
Insights
Plasma MERTK protein is causally linked to increased infection mortality risk. This finding suggests MERTK as a potential therapeutic target for infectious diseases, offering new avenues for treatment.
Area of Science:
- Biochemistry
- Genetics
- Epidemiology
Background:
- Infectious diseases remain a significant global cause of mortality despite existing interventions.
- Identifying reliable biomarkers for infection mortality is crucial for public health strategies.
Purpose of the Study:
- To identify plasma proteins associated with infection mortality.
- To determine if these associations are causally driven using Mendelian randomization (MR).
Main Methods:
- Utilized UK Biobank plasma proteomic data (n=52,520) to associate 2923 proteins with infection mortality.
- Focused on proteins with >1.5-fold increased risk of infection mortality in a survivor-excluded analysis.
- Employed Mendelian randomization (MR) with genome-wide association study (GWAS) data (n=363,953) to assess causality.
Main Results:
- 1142 plasma proteins were associated with infection mortality risk (FDR <0.05).
- 259 proteins showed a >1.5-fold increased risk for infection versus non-infection mortality.
- Increasing MERTK protein concentration was causally associated with increased infection mortality risk (OR 1.46, p=0.002).
Conclusions:
- Plasma MERTK protein is causally linked to infection mortality.
- MERTK represents a potential novel therapeutic target for managing infectious diseases.
