1. TIGER: The gene expression regulatory variation landscape of human pancreatic islets
- Author
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Alonso, Lorena, Piron, Anthony, Morán, Ignasi, Guindo-Martínez, Marta, Bonàs-Guarch, Sílvia, Atla, Goutham, Miguel-Escalada, Irene, Royo, Romina, Puiggròs, Montserrat, Garcia-Hurtado, Xavier, Suleiman, Mara, Marselli, Lorella, Esguerra, Jonathan L.S., Turatsinze, Jean-Valéry, Torres, Jason M., Nylander, Vibe, Chen, Ji, Eliasson, Lena, Defrance, Matthieu, Amela, Ramon, Mulder, Hindrik, Gloyn, Anna L., Groop, Leif, Marchetti, Piero, Eizirik, Decio L., Ferrer, Jorge, Mercader, Josep M., Cnop, Miriam, and Torrents, David
- 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 CCND2expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8variant. 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.
- Published
- 2021
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