Genetic variants influence on the placenta regulatory landscape

PLoS Genet. 2018 Nov 19;14(11):e1007785. doi: 10.1371/journal.pgen.1007785. eCollection 2018 Nov.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Binding Sites / genetics
  • CpG Islands
  • DNA Methylation / genetics
  • Epigenesis, Genetic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Variation*
  • Genome, Human
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Placenta / metabolism*
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Quantitative Trait Loci
  • Sequence Analysis, DNA
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Young Adult


  • Transcription Factors