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

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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 . https://doi.org/10.1038/s41467-020-18581-8

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: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Centre of Excellence in Complex Disease Genetics
Date: 2020-09-30
Language: eng
Number of pages: 14
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/321023
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.
Subject: GENOME-WIDE ASSOCIATION
TYPE-2 DIABETES RISK
BETA-CELL LINE
INSULIN-SECRETION
GLYCEMIC TRAITS
CAUSAL VARIANTS
OPEN CHROMATIN
MESSENGER-RNA
ARCHITECTURE
SIGNATURES
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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