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Using regulatory variants to detect gene-gene interactions identifies networks of genes linked to cell immortalisation.
Wragg, D; Liu, Q; Lin, Z; Riggio, V; Pugh, C A; Beveridge, A J; Brown, H; Hume, D A; Harris, S E; Deary, I J; Tenesa, A; Prendergast, J G D.
Affiliation
  • Wragg D; The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
  • Liu Q; The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
  • Lin Z; The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
  • Riggio V; The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
  • Pugh CA; The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
  • Beveridge AJ; Glasgow Polyomics, College of Medical, Veterinary and Life Science, University of Glasgow, Glasgow, UK.
  • Brown H; The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
  • Hume DA; Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, QLD, 4102, Australia.
  • Harris SE; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
  • Deary IJ; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
  • Tenesa A; The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
  • Prendergast JGD; The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK. James.Prendergast@roslin.ed.ac.uk.
Nat Commun ; 11(1): 343, 2020 01 17.
Article in En | MEDLINE | ID: mdl-31953380
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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lymphocytes / Epistasis, Genetic / Gene Regulatory Networks Type of study: Prognostic_studies Limits: Humans Language: En Journal: Nat Commun Year: 2020 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lymphocytes / Epistasis, Genetic / Gene Regulatory Networks Type of study: Prognostic_studies Limits: Humans Language: En Journal: Nat Commun Year: 2020 Document type: Article