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

Alonso, Lorena ; Piron, Anthony ; Morán, Ignasi ; Guindo-Martínez, Marta ; Bonàs-Guarch, Sílvia ; Atla, Goutham ; Miguel-Escalada, Irene ; Royo, Romina ; Puiggròs, Montserrat and Garcia-Hurtado, Xavier , et al. (2021) In Cell Reports 37(2).
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... (More)

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.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Reports
volume
37
issue
2
article number
109807
publisher
Cell Press
external identifiers
  • scopus:85118520914
  • pmid:34644572
ISSN
2211-1247
DOI
10.1016/j.celrep.2021.109807
language
English
LU publication?
yes
additional info
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
id
59af1f95-4fad-47cc-8239-8adbb9999bfa
date added to LUP
2021-11-12 11:51:10
date last changed
2024-06-15 20:06:03
@article{59af1f95-4fad-47cc-8239-8adbb9999bfa,
  abstract     = {{<p>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 &gt;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 &gt;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.</p>}},
  author       = {{Alonso, Lorena and Piron, Anthony and Morán, Ignasi and Guindo-Martínez, Marta and Bonàs-Guarch, Sílvia and Atla, Goutham and Miguel-Escalada, Irene and Royo, Romina and Puiggròs, Montserrat and Garcia-Hurtado, Xavier and Suleiman, Mara and Marselli, Lorella and Esguerra, Jonathan L S and Turatsinze, Jean-Valéry and Torres, Jason M and Nylander, Vibe and Chen, Ji and Eliasson, Lena and Defrance, Matthieu and Amela, Ramon and Mulder, Hindrik and Gloyn, Anna L and Groop, Leif and Marchetti, Piero and Eizirik, Decio L and Ferrer, Jorge and Mercader, Josep M and Cnop, Miriam and Torrents, David}},
  issn         = {{2211-1247}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{TIGER : The gene expression regulatory variation landscape of human pancreatic islets}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2021.109807}},
  doi          = {{10.1016/j.celrep.2021.109807}},
  volume       = {{37}},
  year         = {{2021}},
}