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A tissue-level phenome-wide network map of colocalized genes and phenotypes in the UK Biobank
- Source :
- Communications Biology. 5
- Publication Year :
- 2022
- Publisher :
- Springer Science and Business Media LLC, 2022.
-
Abstract
- BackgroundPhenome-wide association studies conducted in electronic health record (EHR)-linked biobanks have uncovered a large number of genomic loci associated with traits and diseases. However, interpretation of the complex relationships of associated genes and phenotypes is challenging.ResultsWe constructed a tissue-level phenome-wide network map of colocalized genes and phenotypes. First, we generated colocalized expression quantitative trait loci from 48 tissues of the Genotype-Tissue Expression project and from publicly available genome-wide association study summary statistics from the UK Biobank. We identified 9,151 colocalized genes for 1,411 phenotypes across 48 tissues. Then, we constructed a bipartite network using the colocalized signals to establish links between genes and phenotypes in each tissue. The majority of links are observed in a single tissue whereas only a few are present in all tissues. Finally, we applied the biLouvain clustering algorithm in each tissue-specific bipartite network to identify co-clusters of non-overlapping genes and phenotypes. The majority of co-clusters contains a small number of genes and phenotypes, and 88.6% of co-clusters are found in only one tissue. To demonstrate functionality of the phenome-wide map, we tested if these co-clusters were enriched with known biological and functional gene classes and observed several significant enrichments. Furthermore, we observed that tissue-specific co-clusters are enriched with reported drug side effects for the corresponding drug target genes in clinical trial data.ConclusionsThe phenome-wide map provides links between genes, phenotypes and tissues across a wide spectrum of biological classes and can yield biological and clinical discoveries. The phenome-wide map is publicly available at https://rstudio-connect.hpc.mssm.edu/biPheMap/.
- Subjects :
- Network mapping
Tissue level
Medicine (miscellaneous)
Computational biology
Phenome
Biology
Polymorphism, Single Nucleotide
Phenotype
Biobank
United Kingdom
General Biochemistry, Genetics and Molecular Biology
Expression quantitative trait loci
General Agricultural and Biological Sciences
Gene
Biological Specimen Banks
Genome-Wide Association Study
Genetic association
Subjects
Details
- ISSN :
- 23993642
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Communications Biology
- Accession number :
- edsair.doi.dedup.....ca26d44027fe90184a23e4d97e231da3