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

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-wi...

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Detalles Bibliográficos
Autores principales: Rocheleau, Ghislain, Forrest, Iain S., Duffy, Áine, Bafna, Shantanu, Dobbyn, Amanda, Verbanck, Marie, Won, Hong-Hee, Jordan, Daniel M., Do, Ron
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9392744/
https://www.ncbi.nlm.nih.gov/pubmed/35987940
http://dx.doi.org/10.1038/s42003-022-03820-z
Descripción
Sumario: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.