Genetic variants influence on the placenta regulatory landscape.

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.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Delahaye F,Do C,Kong Y,Ashkar R,Salas M,Tycko B,Wapner R,Hughes F

doi

10.1371/journal.pgen.1007785

subject

Has Abstract

pub_date

2018-11-19 00:00:00

pages

e1007785

issue

11

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-18-00674

journal_volume

14

pub_type

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