Genetic Epidemiology of Preeclampsia

Preeclampsia is a complex hypertensive disorder of pregnancy rooted in both maternal and fetal genetic factors. Familial clustering and twin studies indicate a substantial heritable component, which has driven the application of population genomics and epigenetic profiling to unravel its architecture. Genome-wide association studies and whole-exome sequencing have identified maternal loci shared with blood pressure regulation, placental development and endothelial function, revealing pleiotropic effects on vascular homeostasis. Polygenic risk scores derived from large-scale cohorts capture cumulative burden of risk alleles, offering predictive insights into preeclampsia susceptibility. Epigenetic analyses highlight the role of DNA methylation and imprinted gene expression in trophoblast differentiation and spiral artery remodelling. Emerging work integrates transcriptomic, proteomic and metabolomic data, delineating pathways of immune maladaptation, oxidative stress and angiogenic imbalance at the maternal–fetal interface. Copy-number variants and expression quantitative trait loci further contribute to individual risk, while intergenerational studies suggest inherited predisposition to future cardiovascular disease in offspring and parents. This genetic epidemiology framework underpins stratified screening strategies, informs mechanistic studies of placentation and fosters the development of targeted interventions to mitigate global maternal and perinatal morbidity.

Research from Nature Portfolio

Recent meta-analyses across European and Central Asian cohorts have identified maternal sequence variants at loci such as ZNF831 and FTO that associate with preeclampsia through shared blood pressure pathways. These studies demonstrate that a polygenic risk score for hypertension predicts preeclampsia risk and uncover pleiotropic effects of risk alleles on placental growth, endothelial integrity and proteostasis. The integration of maternal blood pressure variants with placental gene networks has refined the understanding of genetic overlap and highlighted the distinct contribution of pregnancy-specific mechanisms to disease onset.

Genetic Epidemiology of Preeclampsia publication trend

The graph below shows the total number of articles in genetic epidemiology of preeclampsia across all publications each year (not limited to Nature Index journals).

Technical terms

Genome-wide association study (GWAS): A population-based analysis scanning the genome for common variants linked to disease risk.

Polygenic risk score (PRS): A quantitative measure of disease susceptibility calculated from the sum of risk alleles across multiple loci.

Epigenetic reprogramming: The dynamic modification of DNA methylation and histone marks that regulates gene expression without altering the DNA sequence.

Trophoblast: The specialised placental cell lineage essential for embryo implantation and maternal vascular adaptation.

Spiral artery remodelling: The transformation of uterine arteries by trophoblast invasion to ensure adequate placental perfusion.

Expression quantitative trait locus (eQTL): A genomic region where genetic variation influences gene expression levels.

Pleiotropy: The phenomenon by which a single gene or variant affects multiple phenotypic traits.

References

1. Disruption of maternal vascular remodeling by a fetal endoretrovirus-derived gene in preeclampsia. Genome Biology (2024).
2. Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy. JAMA Cardiology (2023).
3. Natriuretic Peptide Signaling in Uterine Biology and Preeclampsia. International Journal of Molecular Sciences (2023).
4. Association between preeclampsia in daughters and risk of cardiovascular disease in parents. European Journal of Epidemiology (2023).
5. The genetic component of preeclampsia: A whole-exome sequencing study. PLOS ONE (2018).
6. Increased Risk of Preeclampsia in Women With a Genetic Predisposition to Elevated Blood Pressure. Hypertension (2022).
7. Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women. Nature Communications (2020).