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Rashmi Prasad

Rashmi Prasad

Assistant researcher

Rashmi Prasad

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

Author

  • Ana Viñuela
  • Arushi Varshney
  • Martijn van de Bunt
  • Rashmi B Prasad
  • Olof Asplund
  • Amanda Bennett
  • Michael Boehnke
  • Andrew A Brown
  • Michael R Erdos
  • João Fadista
  • Ola Hansson
  • Gad Hatem
  • Cédric Howald
  • Apoorva K Iyengar
  • Paul Johnson
  • Ulrika Krus
  • Patrick E MacDonald
  • Anubha Mahajan
  • Jocelyn E Manning Fox
  • Narisu Narisu
  • Vibe Nylander
  • Peter Orchard
  • Nikolay Oskolkov
  • Nikolaos I Panousis
  • Anthony Payne
  • Michael L Stitzel
  • Swarooparani Vadlamudi
  • Ryan Welch
  • Francis S Collins
  • Karen L Mohlke
  • Anna L Gloyn
  • Laura J Scott
  • Emmanouil T Dermitzakis
  • Leif Groop
  • Stephen C J Parker
  • Mark I McCarthy

Summary, in English

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.

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Diabetes - Islet Patophysiology

Publishing year

2020-09-30

Language

English

Pages

4912-4912

Publication/Series

Nature Communications

Volume

11

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 2041-1723