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. 2022 Aug 20;5(1):849.
doi: 10.1038/s42003-022-03820-z.

A tissue-level phenome-wide network map of colocalized genes and phenotypes in the UK Biobank

Ghislain Rocheleau  1   2 , Iain S Forrest  1   2   3 , Áine Duffy  1   2 , Shantanu Bafna  1 , Amanda Dobbyn  1   2   4 , Marie Verbanck  5 , Hong-Hee Won  6 , Daniel M Jordan  1   2 , Ron Do  7   8
Affiliations

A tissue-level phenome-wide network map of colocalized genes and phenotypes in the UK Biobank

Ghislain Rocheleau et al. Commun Biol. .

Abstract

Phenome-wide association studies identified numerous loci associated with traits and diseases. To help interpret these associations, we constructed a phenome-wide network map of colocalized genes and phenotypes. We generated colocalized signals using the Genotype-Tissue Expression data and genome-wide association results in UK Biobank. We identified 9151 colocalized genes for 1411 phenotypes across 48 tissues. Then, we constructed bipartite networks using the colocalized signals in each tissue, and showed that the majority of links were observed in a single tissue. We applied the biLouvain clustering algorithm in each tissue-specific network to identify co-clusters of genes and phenotypes. We observed significant enrichments of these co-clusters with known biological and functional gene classes. Overall, the phenome-wide map provides links between genes, phenotypes and tissues, and can yield biological and clinical discoveries.

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Conflict of interest statement

R.D. received grants from AstraZeneca, grants and nonfinancial support from Goldfinch Bio, is a scientific co-founder, equity holder and consultant for Pensieve Health (pending), and is a consultant for Variant Bio, all not related to this work. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Flowchart of the study.
The flowchart illustrates all the different steps of our study. GWAS genome-wide association study, GTEx Genotype-Tissue Expression, eQTL expression quantitative trait locus.
Fig. 2
Fig. 2. Characteristics of biLouvain co-clusters across tissues.
a Number of genes and phenotypes per co-cluster identified by the biLouvain algorithm. Diamonds are proportional to the frequency of co-cluster size across all 48 tissues. Both axes are displayed on the log scale. b Number of unique co-clusters and how many times they appear in a given number of tissues. y axis is displayed in log scale.
Fig. 3
Fig. 3. PANTHER enrichment analysis of selected biLouvain co-clusters across tissues.
Each panel represents a PANTHER annotation type: (a) Biological process; (b) Cellular component; (c) Molecular function; and (d) Pathway. In each panel, the observed minimal P value across all GO terms is plotted against the expected minimal P value under the null hypothesis of no enrichment for all 183 co-clusters selected. Some plots (a–c) show a breakdown in the y axis to help display very small P values.
See this image and copyright information in PMC

References

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