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 Torres; Vibe Nylander; Ji Chen; Lena Eliasson; Matthieu Defrance; Ramon Amela; MAGIC; Hindrik Mulder; Anna L. Gloyn; Leif Groop; Piero Marchetti; Decio Laks Eizirik; Jorge P. Ferrer; Josep Maria Mercader; Miriam Cnop; David Torrents

doi:10.1016/j.celrep.2021.109807

BioinformaticsCell ReportsOct 1, 2021

Peer-reviewed journal article

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

Lorena Alonso iD, Anthony Piron iD, Ignasi Morán iD, Marta Guindo-Martínez iD, Sílvia Bonàs‐Guarch iD, Goutham Atla iD, Irene Miguel-Escalada iD, Romina Royo iD, Montserrat Puiggròs iD, Xavier Garcia-Hurtado, Mara Suleiman iD, Lorella Marselli iD, Jonathan L.S. Esguerra iD, Jean‐Valéry Turatsinze iD, Jason Torres iD, Vibe Nylander iD, Ji Chen iD, Lena Eliasson iD, Matthieu Defrance iD, Ramon Amela iD, MAGIC, Hindrik Mulder iD, Anna L. Gloyn iD, Leif Groop iD, Piero Marchetti iD, , David Torrents iD

Abstract

GWAS have identified more than 700 genetic signals associated with type 2 diabetes (T2D). To gain insight into the underlying molecular mechanisms, we created the Translational human pancreatic Islet Genotype tissue-Expression Resource (TIGER), aggregating >500 human islet RNA-seq and genotyping datasets. We imputed genotypes using 4 reference panels and meta-analyzed cohorts to improve coverage of expression quantitative trait loci (eQTL) and developed a method to combine allele-specific expression across samples (cASE). We identified >1 million islet eQTLs (56% novel), of which 53 colocalize with T2D signals (60% novel). Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identified 8 novel cASE colocalizations, among which an SLC30A8 T2D associated variant. We make all the data available through the open-access TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translate this into therapeutic insight and precision medicine for T2D.

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