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

Alonso, Lorena; Ferrer, Jorge; Torrents, David

doi:http://dx.doi.org/10.1016/j.celrep.2021.109807

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

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Alonso L, Piron A, Morán I, Guindo-Martínez M, Bonàs-Guarch S, Atla G et al. TIGER: the gene expression regulatory variation landscape of human pancreatic islets. Cell Rep. 2021 Oct 12;37(2):109807. DOI: 10.1016/j.celrep.2021.109807

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.