Genetic variants influence on the placenta regulatory landscape

Area of Science:

• Genomics
• Epigenetics
• Human Placental Biology

Background:

• Understanding genetic-epigenetic interactions is crucial for disease susceptibility and progression.
• Human placental function is vital for fetal development and has implications for maternal and offspring health.
• Current platforms have limitations in integrating diverse genomic data for comprehensive analysis.

Purpose of the Study:

• To investigate the regulatory landscape of the human placenta by analyzing genetic variation, DNA methylation, and mRNA expression.
• To develop and apply analytical approaches for integrating multi-omics data from human placentas.
• To clarify the interactions between genetic, epigenetic, and transcriptional regulatory mechanisms in normal placentas.

Main Methods:

• Collected DNA sequence variation, DNA methylation, and mRNA expression data from 303 (variation and methylation) and 80 (mRNA expression) human placentas.
• Employed high-resolution, whole-genome coverage analysis.
• Developed and utilized analytical approaches to integrate different genomic datasets.

Main Results:

• Distinguished two profiles of interaction between gene expression and DNA methylation: linear and bimodal effects.
• Identified differences in genomic context, transcription factor recruitment, and potential cell subpopulations influencing these interactions.
• Provided strong evidence for genotype-driven modifications of transcription and DNA methylation in normal placentas.

Conclusions:

• The study clarifies the interplay of genetic, epigenetic, and transcriptional regulation in healthy human placentas.
• Findings highlight the significant role of genotype in modulating placental transcription and DNA methylation.
• The presented data and methods enhance the interpretability of genome-wide and epigenome-wide association studies related to placental function and associated diseases.