Genomic insights into gestational weight gain uncover tissue-specific mechanisms and pathways
Year: 2024
Type: article
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 9.37x10⁻⁶). 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.
Source: npj Women s Health
Institutions: Vanderbilt University Medical Center, Vanderbilt University
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,090
Funders: Vanderbilt University, National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Understanding the genetic risk underlying racial disparities in uterine fibroids, Using the Exome to Discover Genetic Determinants of Fibroids in African Americans, The Vanderbilt Institute for Clinical and Translational Research (VICTR) KL2, Large-scale studies in eMERGE to discover the genetic determinants of uterine fibroids, Vanderbilt Integrated Center of Excellence in Maternal and Pediatric Precision Therapeutics (VICE-MPRINT), NRSA Training Core, Building Interdisciplinary Research Careers in Women's Health
OpenAlex ID: W4405121552