ArticlePLoS genetics2022
A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Systematic review and meta-analysis of serum total testosterone and luteinizing hormone variations across hospitalized Covid-19 patients.Scientific reports · 2024Pooled it
- Causal and shared genetic insights into severe COVID-19 and idiopathic pulmonary fibrosis.iScience · 2026Article
- A one-shot, lossless algorithm for cross-cohort learning in mixed-outcomes analysis.Patterns (New York, N.Y.) · 2025Article
- Complex patterns of multimorbidity associated with severe COVID-19 and long COVID.Communications medicine · 2024Article
- Complex patterns of multimorbidity associated with severe COVID-19 and Long COVID.medRxiv : the preprint server for health sciences · 2024Article
- Phenome-wide association study and precision medicine of cardiovascular diseases in the post-COVID-19 era.Acta pharmacologica Sinica · 2023Review
- Leveraging the Million Veteran Program Infrastructure and Data for a Rapid Research Response to COVID-19.Federal practitioner : for the health care professionals of the VA, DoD, and PHS · 2023Article
- Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits.BMC genomics · 2023Article
- Immunohematologic Biomarkers in COVID-19: Insights into Pathogenesis, Prognosis, and Prevention.Pathogens & immunity · 2023Review
- Reply to: Sookaromdee and Wiwanitkit.American journal of respiratory and critical care medicine · 2023Article
- Shared genetics and causal relationships between major depressive disorder and COVID-19 related traits: a large-scale genome-wide cross-trait meta-analysis.Frontiers in psychiatry · 2023Article
- Review
- The US Department of Veterans Affairs Science and Health Initiative to Combat Infectious and Emerging Life-Threatening Diseases (VA SHIELD): A Biorepository Addressing National Health Threats.Open forum infectious diseases · 2022Article
- A Case-Crossover Phenome-wide association study (PheWAS) for understanding Post-COVID-19 diagnosis patterns.Journal of biomedical informatics · 2022Article
- Predicting COVID-19 disease severity from SARS-CoV-2 spike protein sequence by mixed effects machine learning.Computers in biology and medicine · 2022Article
- A Population-Level Analysis of the Protective Effects of Androgen Deprivation Therapy Against COVID-19 Disease Incidence and Severity.Frontiers in medicine · 2022Article
- COVID-19 is associated with the risk of cardiovascular disease death: A two-sample Mendelian randomization study.Frontiers in cardiovascular medicine · 2022Article
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Authors and funding
37 authors at 17 institutions in 2 countries.
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Abstract
The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with critical illness (n = 35) or hospitalization (n = 42) due to severe COVID-19 using genome-wide association summary data from the Host Genetics Initiative. PheWAS analysis was performed using genotype-phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes. Variants at the ABO locus (rs495828, rs505922) associated with the largest number of phenotypes (nrs495828 = 53 and nrs505922 = 59); strongest association with venous embolism, odds ratio (ORrs495828 1.33 (p = 1.32 x 10-199), and thrombosis ORrs505922 1.33, p = 2.2 x10-265. Among 67 respiratory conditions tested, 11 had significant associations including MUC5B locus (rs35705950) with increased risk of idiopathic fibrosing alveolitis OR 2.83, p = 4.12 × 10-191; CRHR1 (rs61667602) associated with reduced risk of pulmonary fibrosis, OR 0.84, p = 2.26× 10-12. The TYK2 locus (rs11085727) associated with reduced risk for autoimmune conditions, e.g., psoriasis OR 0.88, p = 6.48 x10-23, lupus OR 0.84, p = 3.97 x 10-06. PheWAS stratified by ancestry demonstrated differences in genotype-phenotype associations. LMNA (rs581342) associated with neutropenia OR 1.29 p = 4.1 x 10-13 among Veterans of African and Hispanic ancestry but not European. Overall, we observed a shared genetic architecture between COVID-19 severity and conditions related to underlying risk factors for severe and poor COVID-19 outcomes. Differing associations between genotype-phenotype across ancestries may inform heterogenous outcomes observed with COVID-19. Divergent associations between risk for severe COVID-19 with autoimmune inflammatory conditions both respiratory and non-respiratory highlights the shared pathways and fine balance of immune host response and autoimmunity and caution required when considering treatment targets.
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