ArticleGenome medicine2021
An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility.
Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 5 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Pooled it
- Genomic data-driven framework for drug target discovery in atrial fibrillation.Journal of translational medicine · 2025Pooled it
- Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation.Nature communications · 2024Pooled it
- Uncovering associations between pre-existing conditions and COVID-19 Severity: A polygenic risk score approach across three large biobanks.PLoS genetics · 2023Pooled it
- Pooled it
- Disentangling Shared and Differential Genetic Architectures Between COVID-19 and Other Respiratory Disorders-A Genome-Wide Multi-Omics Framework.International journal of molecular sciences · 2026Article
- Integrating single-cell sQTL mapping with deep-learning splicing prediction identifies causal variants under influenza infection.Genome biology · 2026Article
- DPP9-mediated inflammasome repression protects against checkpoint inhibitor lung toxicity.bioRxiv : the preprint server for biology · 2026Article
- Identification and functional characterization of regulatory variants in DPP9 associated with COVID-19 severity.Genome medicine · 2026Article
- Article
- Single-cell multi-omic integration analysis prioritizes druggable genes and reveals cell-type-specific causal effects in glioblastomagenesis.Journal of translational medicine · 2026Article
- Causal and shared genetic insights into severe COVID-19 and idiopathic pulmonary fibrosis.iScience · 2026Article
- Transcriptional mechanisms of sex-biased gene expression and their connections to disease-associated variation.Human molecular genetics · 2026Article
- Causal splicing variants revealed by deep-learning integration of single-cell sQTL mapping under influenza infection.Research square · 2026Article
- Integrating population-level and cell-based signatures for drug repositioning.Bioinformatics (Oxford, England) · 2025Article
- Pattern recognition receptor-associated immuno-thrombotic transcript changes in platelets and leukocytes with COVID19.PLoS pathogens · 2025Article
- A machine learning and centrifugal microfluidics platform for bedside prediction of sepsis.Nature communications · 2025Article
- The multifunctional regulatory post-proline protease dipeptidyl peptidase 9 and its inhibitors: new opportunities for therapeutics.Cellular and molecular life sciences : CMLS · 2025Review
- Identification of potential drug targets for pelvic organ prolapse using a proteome-wide Mendelian randomization approach.Scientific reports · 2025Article
- Genetic evidence for the causal effect of clonal hematopoiesis on pulmonary arterial hypertension.BMC cardiovascular disorders · 2025Article
Corrections and comments
- Update of
Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWhile genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challenge. Methods are needed to systematically bridge this crucial gap to facilitate experimental testing of hypotheses and translation to clinical utility.
resultsHere, we leveraged cross-phenotype associations to identify traits with shared genetic architecture, using linkage disequilibrium (LD) information to accurately capture shared SNPs by proxy, and calculate significance of enrichment. This shared genetic architecture was examined across differing biological scales through incorporating data from catalogs of clinical, cellular, and molecular GWAS. We have created an interactive web database (interactive Cross-Phenotype Analysis of GWAS database (iCPAGdb)) to facilitate exploration and allow rapid analysis of user-uploaded GWAS summary statistics. This database revealed well-known relationships among phenotypes, as well as the generation of novel hypotheses to explain the pathophysiology of common diseases. Application of iCPAGdb to a recent GWAS of severe COVID-19 demonstrated unexpected overlap of GWAS signals between COVID-19 and human diseases, including with idiopathic pulmonary fibrosis driven by the DPP9 locus. Transcriptomics from peripheral blood of COVID-19 patients demonstrated that DPP9 was induced in SARS-CoV-2 compared to healthy controls or those with bacterial infection. Further investigation of cross-phenotype SNPs associated with both severe COVID-19 and other human traits demonstrated colocalization of the GWAS signal at the ABO locus with plasma protein levels of a reported receptor of SARS-CoV-2, CD209 (DC-SIGN). This finding points to a possible mechanism whereby glycosylation of CD209 by ABO may regulate COVID-19 disease severity.
conclusionsThus, connecting genetically related traits across phenotypic scales links human diseases to molecular and cellular measurements that can reveal mechanisms and lead to novel biomarkers and therapeutic approaches. The iCPAGdb web portal is accessible at http://cpag.oit.duke.edu and the software code at https://github.com/tbalmat/iCPAGdb .
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.