TIGER: The gene expression regulatory variation landscape of human pancreatic islets
Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human is...
| Autores: | , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/355658 |
| Acceso en línea: | https://hdl.handle.net/2117/355658 https://dx.doi.org/10.1016/j.celrep.2021.109807 |
| Access Level: | acceso abierto |
| Palabra clave: | Pancreatic islets Gene expression. Expression quantitative trait locus (eQTL) RNA-seq Regulatory variation Epigenomics Allele-specific expression Type 2 diabetes Beta cell Genome-wide association study (GWAS) Transcriptome Genòmica -- Informàtica Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica |
| Sumario: | Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D. |
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