Quantitative trait locus mapping in placenta: A comparative study of chorionic villus and birth placenta

Linda Dieckmann, Marius Lahti-Pulkkinen, Cristiana Cruceanu, Katri Räikkönen, Elisabeth B. Binder, Darina Czamara

Research output: Contribution to journalArticleScientificpeer-review

Abstract

The placenta, a pivotal player in the prenatal environment, holds crucial insights into early developmental pathways and future health outcomes. In this study, we explored genetic molecular regulation in chorionic villus samples (CVS) from the first trimester and placenta tissue at birth. We assessed quantitative trait locus (QTL) mapping on DNA methylation and gene expression data in a Finnish cohort of 574 individuals. We found more QTLs in birth placenta than in first-trimester placenta. Nevertheless, a substantial amount of associations overlapped in their effects and showed consistent direction in both tissues, with increasing molecular genetic effects from early pregnancy to birth placenta. The identified QTLs in birth placenta were most enriched in genes with placenta-specific expression. Conducting a phenome-wide-association study (PheWAS) on the associated SNPs, we observed numerous overlaps with genome-wide association study (GWAS) hits (spanning 57 distinct traits and 23 SNPs), with notable enrichments for immunological, skeletal, and respiratory traits. The QTL-SNP rs1737028 (chr6:29737993) presented with the highest number of GWAS hits. This SNP was related to HLA-G expression via DNA methylation and was associated with various immune, respiratory, and psychiatric traits. Our findings implicate increasing genetic molecular regulation during the course of pregnancy and support the involvement of placenta gene regulation, particularly in immunological traits. This study presents a framework for understanding placenta-specific gene regulation during pregnancy and its connection to health-related traits.

Original languageEnglish
Article number100326
JournalHuman Genetics and Genomics Advances
Volume5
Issue number4
Number of pages17
ISSN2666-2477
DOIs
Publication statusPublished - 10 Oct 2024
MoE publication typeA1 Journal article-refereed

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Fields of Science

  • CVS
  • molecular trait
  • PheWAS
  • placenta
  • QTL
  • 3123 Gynaecology and paediatrics

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