Exphewas: A Browser For Gene-Based Phewas Associations

Motivation The relationship between protein coding genes and phenotypes has the potential to inform on the underlying molecular function in disease etiology. We conducted a phenome-wide association study (pheWAS) of protein coding genes using a principal components analysis-based approach in the UK Biobank. Results We tested the association between 19,114 protein coding gene regions and 1,210 phenotypes including anthropometric measurements, laboratory biomarkers, cancer registry data, hospitalization and death record codes and algorithmically-defined cardiovascular outcomes. We report the pheWAS results in a user-friendly web-based browser. Taking atrial fibrillation, a common cardiac arrhythmia, as an example, ExPheWas identified genes that are known drug targets for the treatment of arrhythmias and genes involved in biological processes implicated in cardiac muscle function. We also identified MYOT as a possible atrial fibrillation gene. Availability and implementation The ExPheWas browser and API are available at Contact Marie-Pierre.Dube{at}mhi-rc.org ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The work was supported by the Health Collaboration Acceleration Fund from the Government of Quebec. MAL holds a scholarship from Canadian Institutes of Health Research (CIHR); MPD holds the Canada Research Chair in Precision medicine data analysis. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The UK Biobank was approved by the relevant ethics committees . This project was evaluated and approved by the Montreal Heart Institute Institutional Review Board under project #2019-2435. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Access to the UK Biobank resource requires application through the Access Management System and instruction are available online: . The ExPheWas results browser is available online at and instructions for programmatic access through the API are provided in the documentation section. The code for the results browser including the database models, the web application and the data visualizations is open source and available at .