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

Show full item record



Vinuela , A , Varshney , A , van de Bunt , M , Prasad , R B , Asplund , O , Bennett , A , Boehnke , M , Brown , A A , Erdos , M R , Fadista , J , Hansson , O , Hatem , G , Howald , C , Iyengar , A K , Johnson , P , Krus , U , MacDonald , P E , Mahajan , A , Manning Fox , J E , Narisu , N , Nylander , V , Orchard , P , Oskolkov , N , Panousis , N I , Payne , A , Stitzel , M L , Vadlamudi , S , Welch , R , Collins , F S , Mohlke , K L , Gloyn , A L , Scott , L J , Dermitzakis , E T , Groop , L , Parker , S C J & McCarthy , M I 2020 , ' Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D ' , Nature Communications , vol. 11 , no. 1 , 4912 .

Title: Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D
Author: Vinuela, Ana; Varshney, Arushi; van de Bunt, Martijn; Prasad, Rashmi B.; Asplund, Olof; Bennett, Amanda; Boehnke, Michael; Brown, Andrew A.; Erdos, Michael R.; Fadista, Joao; Hansson, Ola; Hatem, Gad; Howald, Cedric; Iyengar, Apoorva K.; Johnson, Paul; Krus, Ulrika; MacDonald, Patrick E.; Mahajan, Anubha; Manning Fox, Jocelyn E.; Narisu, Narisu; Nylander, Vibe; Orchard, Peter; Oskolkov, Nikolay; Panousis, Nikolaos I.; Payne, Anthony; Stitzel, Michael L.; Vadlamudi, Swarooparani; Welch, Ryan; Collins, Francis S.; Mohlke, Karen L.; Gloyn, Anna L.; Scott, Laura J.; Dermitzakis, Emmanouil T.; Groop, Leif; Parker, Stephen C. J.; McCarthy, Mark I.
Contributor organization: Institute for Molecular Medicine Finland
University of Helsinki
Centre of Excellence in Complex Disease Genetics
HUS Abdominal Center
University Management
Date: 2020-09-30
Language: eng
Number of pages: 14
Belongs to series: Nature Communications
ISSN: 2041-1723
Abstract: 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.
3111 Biomedicine
1184 Genetics, developmental biology, physiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

Files in this item

Total number of downloads: Loading...

Files Size Format View
s41467_020_18581_8.pdf 4.342Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record