Rxivist logo

Identification of causal drivers behind regulatory gene networks is crucial in understanding gene function. We developed 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). The analysis of genotype and whole-blood RNA-sequencing data from 3,072 individuals identified 49 genes as drivers of downstream transcriptional changes (P < 7 x 10-10), among which transcription factors were overrepresented (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 (novel 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 6,600 genes with a genetic instrument can be explored individually using a web-based browser.

Download data

  • Downloaded 638 times
  • Download rankings, all-time:
    • Site-wide: 18,433 out of 76,817
    • In genomics: 2,224 out of 5,046
  • Year to date:
    • Site-wide: 65,519 out of 76,817
  • Since beginning of last month:
    • Site-wide: 66,696 out of 76,817

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News