Genomic Insights into Gestational Weight Gain: Uncovering Tissue-Specific Mechanisms and Pathways

TL;DR

This study explores how genetic factors and tissue-specific biological pathways may influence weight gain during pregnancy, revealing potential mechanisms that vary by tissue and gestation stage.

Contribution

The study identifies tissue-specific biological pathways enriched for genes related to gestational weight gain, offering new insights into its genetic and biological underpinnings.

Findings

No significant associations were found between maternal and fetal gene expression and gestational weight gain after multiple testing correction.

Biological pathways like metabolic processes, secretion, and intracellular transport were enriched in maternal tissues related to gestational weight gain.

Enriched pathways varied across pregnancy stages, suggesting dynamic biological influences on gestational weight gain.

Abstract

Increasing gestational weight gain (GWG) is linked to adverse outcomes in pregnant persons and their children. The Early Growth Genetics (EGG) Consortium identified previously genetic variants that could contribute to early, late, and total GWG from fetal and maternal genomes. However, the biologic mechanisms and tissue-Specificity of these variants in GWG is unknown. We evaluated the association between genetically predicted gene expression in five relevant maternal (subcutaneous and visceral adipose, breast, uterus, and whole blood) from GTEx (v7) and fetal (placenta) tissues and early, late, and total GWG using S-PrediXcan. We tested enrichment of pre-defined biological pathways for nominally (P < 0.05) significant associations using the GENE2FUNC module from Functional Mapping and Annotation of Genome-Wide Association Studies. After multiple testing correction, we did not find significant associations between maternal and fetal gene expression and early, late, or total GWG. There was significant enrichment of several biological pathways, including metabolic processes, secretion, and intracellular transport, among nominally significant genes from the maternal analyses (false discovery rate p-values: 0.016 to 9.37×10). Enriched biological pathways varied across pregnancy. Though additional research is necessary, these results indicate that diverse biological pathways are likely to impact GWG, with their influence varying by tissue and weeks of gestation.

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