TIGER: The gene expression regulatory variation landscape of human pancreatic islets
dc.contributor.author | Alonso, L | |
dc.contributor.author | Piron, A | |
dc.contributor.author | Morán, I | |
dc.contributor.author | Guindo-Martínez, M | |
dc.contributor.author | Bonàs-Guarch, S | |
dc.contributor.author | Atla, G | |
dc.contributor.author | Miguel-Escalada, I | |
dc.contributor.author | Royo, R | |
dc.contributor.author | Puiggròs, M | |
dc.contributor.author | Garcia-Hurtado, X | |
dc.contributor.author | Suleiman, M | |
dc.contributor.author | Marselli, L | |
dc.contributor.author | Esguerra, JLS | |
dc.contributor.author | Turatsinze, JV | |
dc.contributor.author | Torres, JM | |
dc.contributor.author | Nylander, V | |
dc.contributor.author | Chen, J | |
dc.contributor.author | Eliasson, L | |
dc.contributor.author | Defrance, M | |
dc.contributor.author | Amela, R | |
dc.contributor.author | MAGIC | |
dc.contributor.author | Mulder, H | |
dc.contributor.author | Gloyn, AL | |
dc.contributor.author | Groop, L | |
dc.contributor.author | Marchetti, P | |
dc.contributor.author | Eizirik, DL | |
dc.contributor.author | Ferrer, J | |
dc.contributor.author | Mercader, JM | |
dc.contributor.author | Cnop, M | |
dc.contributor.author | Torrents, D | |
dc.date.accessioned | 2021-09-21T07:36:10Z | |
dc.date.issued | 2021-10-12 | |
dc.description.abstract | 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. | en_GB |
dc.identifier.citation | Vol. 37 (2), article 109807 | en_GB |
dc.identifier.doi | 10.1016/j.celrep.2021.109807 | |
dc.identifier.uri | http://hdl.handle.net/10871/127151 | |
dc.language.iso | en | en_GB |
dc.publisher | Cell Press | en_GB |
dc.rights | © 2021 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) | |
dc.subject | Expression quantitative trait locus (eQTL) | en_GB |
dc.subject | pancreatic islets | en_GB |
dc.subject | RNA-seq | en_GB |
dc.subject | regulatory variation | en_GB |
dc.subject | epigenomics | en_GB |
dc.subject | allele-specific expression | en_GB |
dc.subject | type 2 diabetes | en_GB |
dc.title | TIGER: The gene expression regulatory variation landscape of human pancreatic islets | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2021-09-21T07:36:10Z | |
dc.identifier.issn | 2211-1247 | |
dc.description | This is the final version. Available on open access from Elsevier via the DOI in this record | en_GB |
dc.description | RNA-seq and genotyping array data from PISA cohort Sequence data has been deposited at the European Genome-phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001005535. Further information about EGA can be found on https://ega-archive.org "The European Genome-phenome Archive of human data consented for biomedical research"(http://www.nature.com/ng/journal/v47/n7/full/ng.3312.html ). RNA-seq and genotyping array data from CRG cohort should be requested through Miguel-Escalada, I. et al (2019) and Atla, G. et al (unpublished). The eQTL and cASE results are available for browsing at TIGER (http://tiger.bsc.es) and the full summary statistics are available for download. Source data and publicly available resources used for this study supporting all findings are detailed in Suppl. Resources Table. The cASE code is available through https://github.com/imoran-BSC/TIGER_cASE. Any additional information required to reanalyze the data reported in this work paper is available from the Lead Contact upon request. | en_GB |
dc.identifier.journal | Cell Reports | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_GB |
dcterms.dateAccepted | 2021-09-16 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2021-09-16 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2021-09-20T16:01:53Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2021-11-05T15:56:50Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © 2021 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)