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Hindrik Mulder

Hindrik Mulder

Principal investigator

Hindrik Mulder

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

Author

  • 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 M Torres
  • Vibe Nylander
  • Ji Chen
  • Lena Eliasson
  • Matthieu Defrance
  • Ramon Amela
  • Hindrik Mulder
  • Anna L Gloyn
  • Leif Groop
  • Piero Marchetti
  • Decio L Eizirik
  • Jorge Ferrer
  • Josep M Mercader
  • Miriam Cnop
  • David Torrents

Summary, in English

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.

Department/s

  • Diabetes - Islet Cell Exocytosis
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Diabetes - Molecular Metabolism
  • Genomics, Diabetes and Endocrinology

Publishing year

2021

Language

English

Publication/Series

Cell Reports

Volume

37

Issue

2

Document type

Journal article

Publisher

Cell Press

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis
  • Diabetes - Molecular Metabolism
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 2211-1247