ArticleBMC medicine2021
Placenta mediates the effect of maternal hypertension polygenic score on offspring birth weight: a study of birth cohort with fetal growth velocity data.
Article in BMC medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 21 citations in OpenAlex.
- Association between three-timepoint maternal blood pressure trajectories during pregnancy and low birth weight: a longitudinal study based on NHANES 2005-2006.Frontiers in pediatrics · 2025Article
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- Prenatal vitamin D deficiency exposure leads to long-term changes in immune cell proportions.Scientific reports · 2024Article
- Reconsidering the developmental origins of adult disease paradigm: The 'metabolic coordination of childbirth' hypothesis.Evolution, medicine, and public health · 2024Review
- Heart Rate Variability and Pregnancy Complications: Systematic Review.Interactive journal of medical research · 2023Review
- Diet Quality and Its Relationship with Weight Characteristics in Pregnant Japanese Women: A Single-Center Birth Cohort Study.Nutrients · 2023Article
- Combination of genetic and environmental factors for childhood hypertension: a simple indicator of family history remains useful.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- Combating hypertension beyond genome-wide association studies: Microbiome and artificial intelligence as opportunities for precision medicine.Cambridge prisms. Precision medicine · 2023Review
- Hypertensive disorders of pregnancy: definition, management, and out-of-office blood pressure measurement.Hypertension research : official journal of the Japanese Society of Hypertension · 2022Review
- Genetic variation in placental insufficiency: What have we learned over time?Frontiers in cell and developmental biology · 2022Review
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10 authors at 2 institutions in 2 countries.
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Abstract
backgroundLow birth weight (LBW) and fetal growth restriction are associated with the development of cardio-metabolic diseases later in life. A recent Mendelian randomization study concluded that the susceptibility of LBW infants to develop hypertension during adulthood is due to the inheritance of hypertension genes from the mother and not to an unfavorable intrauterine environment. Therein, a negative linear association has been assumed between genetically estimated maternal blood pressure (BP) and birth weight, while the observed relationship between maternal BP and birth weight is substantially different from that assumption. As many hypertension genes are likely involved in vasculature development and function, we hypothesized that BP-increasing genetic variants could affect birth weight by reducing the growth of the placenta, a highly vascular organ, without overtly elevating the maternal BP.
methodsUsing a birth cohort in the Japanese population possessing time-series fetal growth velocity data as a target and a GWAS summary statistics of BioBank Japan as a base data, we performed polygenic score (PGS) analyses for systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure. A causal mediation analysis was performed to assess the meditation effect of placental weight on birth weight reduced by maternal BP-increasing PGS. Maternal genetic risk score constituted of only "vasculature-related" BP single nucleotide polymorphisms (SNPs) was constructed to examine the involvement of vascular genes in the mediation effect of placental weight. We identified gestational week in which maternal SBP-increasing PGS significantly decreased fetal growth velocity.
resultsWe observed that maternal SBP-increasing PGS was negatively associated with offspring birth weight. A causal mediation analysis revealed that a large proportion of the total maternal PGS effect on birth weight was mediated by placental weight. The placental mediation effect was remarkable when genetic risk score was constituted of "vasculature-related" BP SNPs. The inverse association between maternal SBP PGS and fetal growth velocity only became apparent in late gestation.
conclusionsOur study suggests that maternal hypertension genes are strongly associated with placental growth and that fetal growth inhibition is induced through the intrauterine environment established by the placenta.
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