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

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 Wijmenga, Lude Franke, Peter A. C. ’t Hoen, Rick Jansen, Joyce Meurs, Hailiang Mei, P. Eline Slagboom, Bastiaan T. Heijmans () and Erik W. Zwet ()
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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
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

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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

Date: 2018
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DOI: 10.1038/s41467-018-05452-6

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