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

Alonso, L.; Piron, A.; Moran, I.; Guindo-Martinez, M.; Bonas-Guarch, S.; Atla, G.; Miguel-Escalada, I.; Royo, R.; Puiggros, M.; Garcia-Hurtado, X.; Suleiman, M.; Marselli, L.; Esguerra, J. L. S.; Turatsinze, J.-V.; Torres, J. M.; Nylander, V.; Chen, J.; Eliasson, L.; Defrance, M.; Amela, R.; MAGIC,; Mulder, H.; Gloyn, A. L.; Groop, L.; Marchetti, P.; Eizirik, D. L.; Ferrer, J.; Mercader, J. M.; Cnop, M.; Torrents, D.

doi:10.1101/2021.05.26.445616

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bioRxiv · 10.1101/2021.05.26.445616

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

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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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Alonso, L., Piron, A., Moran, I., Guindo-Martinez, M., Bonas-Guarch, S., Atla, G., Miguel-Escalada, I., Royo, R., Puiggros, M., Garcia-Hurtado, X., Suleiman, M., Marselli, L., Esguerra, J. L. S., Turatsinze, J.-V., Torres, J. M., Nylander, V., Chen, J., Eliasson, L., Defrance, M., Amela, R., MAGIC,, Mulder, H., Gloyn, A. L., Groop, L., Marchetti, P., Eizirik, D. L., Ferrer, J., Mercader, J. M., Cnop, M., Torrents, D.. 2021-05-27. TIGER: The gene expression regulatory variation landscape of human pancreatic islets. https://doi.org/10.1101/2021.05.26.445616

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