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Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D

Lookup NU author(s): Dr Ana ViñuelaORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020, The Author(s). Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in the stretch enhancers most strongly implicated in GWAS signal location; (c) enrichment of islet cis-eQTL signals with T2D risk variants identified in genome-wide association studies; and (d) colocalization between 47 islet cis-eQTLs and variants influencing T2D or glycemic traits, including DGKB and TCF7L2. Our findings illustrate the advantages of performing functional and regulatory studies in disease relevant tissues.

Publication metadata

Author(s): Viñuela A, Varshney A, van de Bunt M, Prasad RB, Asplund O, Bennett A, Boehnke M, Brown AA, Erdos MR, Fadista J, Hansson O, Hatem G, Howald C, Iyengar AK, Johnson P, Krus U, MacDonald PE, Mahajan A, Manning Fox JE, Narisu N, Nylander V, Orchard P, Oskolkov N, Panousis NI, Payne A, Stitzel ML, Vadlamudi S, Welch R, Collins FS, Mohlke KL, Gloyn AL, Scott LJ, Dermitzakis ET, Groop L, Parker SCJ, McCarthy MI

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2020

Volume: 11

Issue: 1

Online publication date: 30/09/2020

Acceptance date: 12/08/2020

Date deposited: 04/01/2021

ISSN (electronic): 2041-1723

Publisher: Nature Research


DOI: 10.1038/s41467-020-18581-8

PubMed id: 32999275


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