Publication

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

BIOS Consortium, Luijk, R., Dekkers, K. F., van Iterson, M., Arindrarto, W., Claringbould, A., Hop, P., Boomsma, D., van Duijn, C. M., van Greevenbroek, M. M. J., Veldink, J. H., Wijmenga, C., Franke, L., 't Hoend, P. A. C., Jansen, R., van Meurs, J., Mei, H., Slagboomi, P. E., Heijmans, B. T. & van Zwet, E. W., 6-Aug-2018, In : Nature Communications. 9, 1, p. 3097 10 p., 3097.

Research output: Contribution to journalArticleAcademicpeer-review

APA

BIOS Consortium, Luijk, R., Dekkers, K. F., van Iterson, M., Arindrarto, W., Claringbould, A., ... van Zwet, E. W. (2018). Genome-wide identification of directed gene networks using large-scale population genomics data. Nature Communications, 9(1), 3097. [3097]. https://doi.org/10.1038/s41467-018-05452-6

Author

BIOS Consortium ; Luijk, Rene ; Dekkers, Koen F. ; van Iterson, Maarten ; Arindrarto, Wibowo ; Claringbould, Annique ; Hop, Paul ; Boomsma, Dorret ; van Duijn, Cornelia M. ; van Greevenbroek, Marleen M. J. ; Veldink, Jan H. ; Wijmenga, Cisca ; Franke, Lude ; 't Hoend, Peter A. C. ; Jansen, Rick ; van Meurs, Joyce ; Mei, Hailiang ; Slagboomi, P. Eline ; Heijmans, Bastiaan T. ; van Zwet, Erik W. / Genome-wide identification of directed gene networks using large-scale population genomics data. In: Nature Communications. 2018 ; Vol. 9, No. 1. pp. 3097.

Harvard

BIOS Consortium, Luijk, R, Dekkers, KF, van Iterson, M, Arindrarto, W, Claringbould, A, Hop, P, Boomsma, D, van Duijn, CM, van Greevenbroek, MMJ, Veldink, JH, Wijmenga, C, Franke, L, 't Hoend, PAC, Jansen, R, van Meurs, J, Mei, H, Slagboomi, PE, Heijmans, BT & van Zwet, EW 2018, 'Genome-wide identification of directed gene networks using large-scale population genomics data', Nature Communications, vol. 9, no. 1, 3097, pp. 3097. https://doi.org/10.1038/s41467-018-05452-6

Standard

Genome-wide identification of directed gene networks using large-scale population genomics data. / BIOS Consortium; Luijk, Rene; Dekkers, Koen F.; van Iterson, Maarten; Arindrarto, Wibowo; Claringbould, Annique; Hop, Paul; Boomsma, Dorret; van Duijn, Cornelia M.; van Greevenbroek, Marleen M. J.; Veldink, Jan H.; Wijmenga, Cisca; Franke, Lude; 't Hoend, Peter A. C.; Jansen, Rick; van Meurs, Joyce; Mei, Hailiang; Slagboomi, P. Eline; Heijmans, Bastiaan T.; van Zwet, Erik W.

In: Nature Communications, Vol. 9, No. 1, 3097, 06.08.2018, p. 3097.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

BIOS Consortium, Luijk R, Dekkers KF, van Iterson M, Arindrarto W, Claringbould A et al. Genome-wide identification of directed gene networks using large-scale population genomics data. Nature Communications. 2018 Aug 6;9(1):3097. 3097. https://doi.org/10.1038/s41467-018-05452-6


BibTeX

@article{767745530e544017bb74f1b246da23d2,
title = "Genome-wide identification of directed gene networks using large-scale population genomics data",
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 <7 x 10(-10)), among which transcription factors were over-represented (Fisher's P = 3.3 x 10(-7)). Our analysis suggests new gene functions and targets, including for SENP7 (zinc-finger genes involved in retroviral repression) and BCL2A1 (target genes possibly involved in auditory dysfunction). Our work highlights the utility of population genomics data in deriving directed gene expression networks. A resource of trans-effects for all 6600 genes with a genetic instrument can be explored individually using a web-based browser.",
keywords = "MENDELIAN RANDOMIZATION, TRANSCRIPTIONAL REGULATION, ENDOGENOUS RETROVIRUSES, INSULIN-SECRETION, HUMAN TISSUES, TRANS-EQTLS, SAMPLE-SIZE, CELL-DEATH, RNA-SEQ, ASSOCIATION",
author = "{BIOS Consortium} and Rene Luijk and Dekkers, {Koen F.} and {van Iterson}, Maarten and Wibowo Arindrarto and Annique Claringbould and Paul Hop and Dorret Boomsma and {van Duijn}, {Cornelia M.} and {van Greevenbroek}, {Marleen M. J.} and Veldink, {Jan H.} and Cisca Wijmenga and Lude Franke and {'t Hoend}, {Peter A. C.} and Rick Jansen and {van Meurs}, Joyce and Hailiang Mei and Slagboomi, {P. Eline} and Heijmans, {Bastiaan T.} and {van Zwet}, {Erik W.}",
year = "2018",
month = "8",
day = "6",
doi = "10.1038/s41467-018-05452-6",
language = "English",
volume = "9",
pages = "3097",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Genome-wide identification of directed gene networks using large-scale population genomics data

AU - BIOS Consortium

AU - Luijk, Rene

AU - Dekkers, Koen F.

AU - van Iterson, Maarten

AU - Arindrarto, Wibowo

AU - Claringbould, Annique

AU - Hop, Paul

AU - Boomsma, Dorret

AU - van Duijn, Cornelia M.

AU - van Greevenbroek, Marleen M. J.

AU - Veldink, Jan H.

AU - Wijmenga, Cisca

AU - Franke, Lude

AU - 't Hoend, Peter A. C.

AU - Jansen, Rick

AU - van Meurs, Joyce

AU - Mei, Hailiang

AU - Slagboomi, P. Eline

AU - Heijmans, Bastiaan T.

AU - van Zwet, Erik W.

PY - 2018/8/6

Y1 - 2018/8/6

N2 - 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 <7 x 10(-10)), among which transcription factors were over-represented (Fisher's P = 3.3 x 10(-7)). Our analysis suggests new gene functions and targets, including for SENP7 (zinc-finger genes involved in retroviral repression) and BCL2A1 (target genes possibly involved in auditory dysfunction). Our work highlights the utility of population genomics data in deriving directed gene expression networks. A resource of trans-effects for all 6600 genes with a genetic instrument can be explored individually using a web-based browser.

AB - 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 <7 x 10(-10)), among which transcription factors were over-represented (Fisher's P = 3.3 x 10(-7)). Our analysis suggests new gene functions and targets, including for SENP7 (zinc-finger genes involved in retroviral repression) and BCL2A1 (target genes possibly involved in auditory dysfunction). Our work highlights the utility of population genomics data in deriving directed gene expression networks. A resource of trans-effects for all 6600 genes with a genetic instrument can be explored individually using a web-based browser.

KW - MENDELIAN RANDOMIZATION

KW - TRANSCRIPTIONAL REGULATION

KW - ENDOGENOUS RETROVIRUSES

KW - INSULIN-SECRETION

KW - HUMAN TISSUES

KW - TRANS-EQTLS

KW - SAMPLE-SIZE

KW - CELL-DEATH

KW - RNA-SEQ

KW - ASSOCIATION

U2 - 10.1038/s41467-018-05452-6

DO - 10.1038/s41467-018-05452-6

M3 - Article

VL - 9

SP - 3097

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 3097

ER -

ID: 65762991