Genetic variants influence on the placenta regulatory landscape

Fabien Delahaye, Catherine Do, Yu Kong, Remi Ashkar, Martha Salas, Ben Tycko, Ronald Wapner, Francine Hughes

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

From genomic association studies, quantitative trait loci analysis, and epigenomic mapping, it is evident that significant efforts are necessary to define genetic-epigenetic interactions and understand their role in disease susceptibility and progression. For this reason, an analysis of the effects of genetic variation on gene expression and DNA methylation in human placentas at high resolution and whole-genome coverage will have multiple mechanistic and practical implications. By producing and analyzing DNA sequence variation (n = 303), DNA methylation (n = 303) and mRNA expression data (n = 80) from placentas from healthy women, we investigate the regulatory landscape of the human placenta and offer analytical approaches to integrate different types of genomic data and address some potential limitations of current platforms. We distinguish two profiles of interaction between expression and DNA methylation, revealing linear or bimodal effects, reflecting differences in genomic context, transcription factor recruitment, and possibly cell subpopulations. These findings help to clarify the interactions of genetic, epigenetic, and transcriptional regulatory mechanisms in normal human placentas. They also provide strong evidence for genotype-driven modifications of transcription and DNA methylation in normal placentas. In addition to these mechanistic implications, the data and analytical methods presented here will improve the interpretability of genome-wide and epigenome-wide association studies for human traits and diseases that involve placental functions.

Original languageEnglish (US)
Article numbere1007785
JournalPLoS Genetics
Volume14
Issue number11
DOIs
StatePublished - Nov 1 2018

Fingerprint

placenta
Placenta
methylation
DNA methylation
DNA Methylation
DNA
Epigenomics
epigenetics
genomics
Placenta Diseases
genome
Genome
Quantitative Trait Loci
Disease Susceptibility
subpopulation
disease course
gene expression
analytical methods
disease resistance
Disease Progression

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Delahaye, F., Do, C., Kong, Y., Ashkar, R., Salas, M., Tycko, B., ... Hughes, F. (2018). Genetic variants influence on the placenta regulatory landscape. PLoS Genetics, 14(11), [e1007785]. https://doi.org/10.1371/journal.pgen.1007785

Genetic variants influence on the placenta regulatory landscape. / Delahaye, Fabien; Do, Catherine; Kong, Yu; Ashkar, Remi; Salas, Martha; Tycko, Ben; Wapner, Ronald; Hughes, Francine.

In: PLoS Genetics, Vol. 14, No. 11, e1007785, 01.11.2018.

Research output: Contribution to journalArticle

Delahaye, F, Do, C, Kong, Y, Ashkar, R, Salas, M, Tycko, B, Wapner, R & Hughes, F 2018, 'Genetic variants influence on the placenta regulatory landscape', PLoS Genetics, vol. 14, no. 11, e1007785. https://doi.org/10.1371/journal.pgen.1007785
Delahaye F, Do C, Kong Y, Ashkar R, Salas M, Tycko B et al. Genetic variants influence on the placenta regulatory landscape. PLoS Genetics. 2018 Nov 1;14(11). e1007785. https://doi.org/10.1371/journal.pgen.1007785
Delahaye, Fabien ; Do, Catherine ; Kong, Yu ; Ashkar, Remi ; Salas, Martha ; Tycko, Ben ; Wapner, Ronald ; Hughes, Francine. / Genetic variants influence on the placenta regulatory landscape. In: PLoS Genetics. 2018 ; Vol. 14, No. 11.
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