1. Publications

TIGER: The gene expression regulatory variation landscape of human pancreatic islets

Lorena Alonso, Anthony Piron, Ignasi Morán, Marta Guindo-Martínez, Sílvia Bonàs-Guarch, Goutham Atla, Irene Miguel-Escalada, Romina Royo, Montserrat Puiggròs, Xavier Garcia-Hurtado, Mara Suleiman, Lorella Marselli, Jonathan L S Esguerra, Jean-Valéry Turatsinze, Jason M Torres, Vibe Nylander, Ji Chen, Lena Eliasson, Matthieu Defrance, Ramon Amela; MAGIC; Hindrik Mulder, Anna L Gloyn, Leif Groop, Piero Marchetti, Decio L Eizirik, Jorge Ferrer, Josep M Mercader, Miriam Cnop, David Torrents.
Cell Rep. 2021-10-12;37(2):109807.
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.

Related data

Data summary
RNA-seq and genotyping array data from PISA cohort Sequence data have 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”( https://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 et al. (2019 ) and coauthor Goutham Atla. 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 the key 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.