Using regulatory variants to detect gene-gene interactions identifies networks of genes linked to cell immortalization

David Wragg, Qian Liu, Zeng Lin, Valentina Riggio, Carys Pugh, Allan Beveridge, Helen Brown, David Hume, Sarah Harris, Ian Deary, Albert Tenesa, James Prendergast

Research output: Contribution to journalArticlepeer-review

Abstract

The extent to which the impact of regulatory genetic variants may depend on other factors, such as the expression levels of upstream transcription factors, remains poorly understood. Here we report a framework in which regulatory variants are first aggregated into sets, and using these as estimates of the total cis-genetic effects on a gene we model their non-additive interactions with the expression of other genes in the genome. Using 1220 lymphoblastoid cell lines across platforms and independent datasets we identify 74 genes where the impact of their regulatory variant-set is linked to the expression levels of networks of distal genes. We show that these networks are predominantly associated with tumourigenesis pathways, through which immortalised cells are able to rapidly proliferate. We consequently present an approach to define gene interaction networks underlying important cellular pathways such as cell immortalisation.
Original languageEnglish
Article number343
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 17 Jan 2020

Keywords

  • gene expression
  • gene regulation
  • genetic interaction
  • haplotypes

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