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Genome-wide identification of directed gene networks using large-scale population genomics data

Author

Listed:
  • René Luijk

    (Leiden University Medical Center, Leiden)

  • Koen F. Dekkers

    (Leiden University Medical Center, Leiden)

  • Maarten Iterson

    (Leiden University Medical Center, Leiden)

  • Wibowo Arindrarto

    (Leiden University Medical Center, Leiden)

  • Annique Claringbould

    (University of Groningen, University Medical Centre Groningen)

  • Paul Hop

    (Leiden University Medical Center, Leiden)

  • Dorret I. Boomsma

    (VU University Amsterdam)

  • Cornelia M. Duijn

    (ErasmusMC)

  • Marleen M. J. Greevenbroek

    (Maastricht University Medical Center
    Maastricht University Medical Center)

  • Jan H. Veldink

    (University Medical Center Utrecht)

  • Cisca Wijmenga

    (University of Groningen, University Medical Centre Groningen)

  • Lude Franke

    (University of Groningen, University Medical Centre Groningen)

  • Peter A. C. ’t Hoen

    (Leiden University Medical Center, Leiden)

  • Rick Jansen

    (VU University Medical Center)

  • Joyce Meurs

    (ErasmusMC)

  • Hailiang Mei

    (Leiden University Medical Center, Leiden)

  • P. Eline Slagboom

    (Leiden University Medical Center, Leiden)

  • Bastiaan T. Heijmans

    (Leiden University Medical Center, Leiden)

  • Erik W. Zwet

    (Leiden University Medical Center, Leiden)

Abstract

Identification of causal drivers behind regulatory gene networks is crucial in understanding gene function. Here, we develop a method for the large-scale inference of gene–gene interactions in observational population genomics data that are both directed (using local genetic instruments as causal anchors, akin to Mendelian Randomization) and specific (by controlling for linkage disequilibrium and pleiotropy). Analysis of genotype and whole-blood RNA-sequencing data from 3072 individuals identified 49 genes as drivers of downstream transcriptional changes (Wald P

Suggested Citation

  • René Luijk & Koen F. Dekkers & Maarten Iterson & Wibowo Arindrarto & Annique Claringbould & Paul Hop & Dorret I. Boomsma & Cornelia M. Duijn & Marleen M. J. Greevenbroek & Jan H. Veldink & Cisca Wijme, 2018. "Genome-wide identification of directed gene networks using large-scale population genomics data," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05452-6
    DOI: 10.1038/s41467-018-05452-6
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