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

par 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;MAGIC, Hindrik;Mulder, Anna L;Gloyn, Leif;Groop, Piero;Marchetti, Decio L.;Eizirik, Jorge ;Ferrer, Josep JM;Mercader, Miriam;Cnop, David ;Torrents,
Référence Cell reports, 37, 2, page (109807)
Publication Publié, 2021-10-01

Article révisé par les pairs

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Résumé :

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.