TIGER : The gene expression regulatory variation landscape of human pancreatic islets
(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.
(Less)
- author
- author collaboration
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell Reports
- volume
- 37
- issue
- 2
- article number
- 109807
- publisher
- Cell Press
- external identifiers
-
- pmid:34644572
- scopus:85118520914
- 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 >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.</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}}, }