
==== Front
medRxiv
MEDRXIV
medRxiv
Cold Spring Harbor Laboratory

10.1101/2024.08.26.24312498
preprint
1
Article
Electronic health record biobank cohort recapitulates an association between the MUC5B promoter polymorphism and ARDS in critically ill adults
Kerchberger V. Eric http://orcid.org/0000-0002-0342-1965

McNeil J. Brennan http://orcid.org/0000-0002-9200-1881

Zheng Neil http://orcid.org/0000-0001-8737-0773

Chang Diana http://orcid.org/0000-0002-0832-7177

Rosenberger Carrie http://orcid.org/0000-0002-8189-8822

Rogers Angela J. http://orcid.org/0000-0001-6969-6200

Bastarache Julie A. http://orcid.org/0000-0003-0458-6507

Feng QiPing http://orcid.org/0000-0002-6213-793X

Wei Wei-Qi http://orcid.org/0000-0003-4985-056X

Ware Lorraine B. http://orcid.org/0000-0002-9429-4702

26 8 2024
2024.08.26.24312498https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://medrxiv.org/lookup/doi/10.1101/2024.08.26.24312498
nihpp-2024.08.26.24312498.pdf
ABSTRACT

Background

Large population-based DNA biobanks linked to electronic health records (EHRs) may provide advantages over traditional study designs for identifying genetic drivers of ARDS.

Research Question

Can ARDS be identified in an EHR biobank, and can this approach validate a previously reported genetic risk factor for ARDS?

Study Design and Methods

We analyzed two genotyped cohorts from one academic medical center: a prospective biomarker study of critically ill adults (VALID cohort), and hospitalized participants in a de-identified EHR biobank (BioVU). ARDS status was assessed by clinician-investigator review in VALID and an EHR-derived algorithm in BioVU (EHR-ARDS). We tested the association between the MUC5B promoter polymorphism (rs35705950) with development of ARDS/EHR-ARDS in each cohort.

Results

In VALID, 2,795 patients were included, age was 55 [43, 66] (median [IQR]) years, and 718 (25.7%) developed ARDS. In BioVU, 9,025 hospitalized participants were included, age was 60 [48, 70] , and 1,056 (11.7%) developed EHR-ARDS. We observed a significant interaction between age and rs35705950 on ARDS risk in VALID: in older patients rs35705950 was associated with increased ARDS risk (OR: 1.44; 95%CI 1.08-1.92; p=0.012) whereas among younger patients this effect was attenuated (OR: 0.84; 95%CI: 0.62-1.14; p=0.26). In BioVU, rs35705950 was associated with increased risk for EHR-ARDS among all participants (OR: 1.20; 95%CI: 1.00-1.43, p=0.043) and this relationship did not vary by age. The polymorphism was also associated with more severe oxygenation impairment among BioVU participants who required mechanical ventilation.

Interpretation

The MUC5B promoter polymorphism was associated with ARDS in two cohorts of at-risk hospitalized adults. Although age-related effect modification was observed only in the prospective biomarker cohort, the EHR cohort identified a consistent association between MUC5B and ARDS risk regardless of age and a novel association with oxygenation impairment. Our study highlights the potential for EHR biobanks to enable precision-medicine ARDS studies.
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