Biology Insights

Is Preeclampsia Genetic? A Look at Its Causes and Risks

Uncover the intricate blend of hereditary influences and environmental factors that shape the risk and manifestation of preeclampsia.

By Keisha Kamau

Preeclampsia has a clear genetic component, but it is not caused by a single inherited gene the way some conditions are. The best estimates put its heritability at roughly 30%, meaning that about a third of the variation in who develops preeclampsia can be traced to genetic differences rather than environment or chance. The rest of the story involves immune responses, blood vessel function, the placenta, the father’s genes, and a long list of clinical risk factors. Understanding how all these threads weave together matters, because preeclampsia affects somewhere between 3% and 10% of pregnancies worldwide and remains a leading cause of serious complications for both mother and baby.

How Strong Is the Family Link

If your mother or sister had preeclampsia, your own risk goes up substantially. A large Scandinavian family study estimated the heritability of preeclampsia at about 31%, with full sisters sharing a much higher risk than half-sisters. Full sisters had roughly triple the odds of both developing preeclampsia, while maternal half-sisters showed a weaker and statistically uncertain association, and paternal half-sisters showed essentially no increased risk at all. A separate U.S.-based study found that women who had experienced preeclampsia were about 2.3 times more likely to have a sister who also had it, a pattern that held regardless of age, race, smoking status, or body weight.

The fact that full sisters share more risk than half-sisters, and that the pattern persists after adjusting for shared lifestyle factors, points strongly toward genetics rather than a shared household environment. But the flip side is equally telling: 31% heritability means nearly 70% of the picture comes from somewhere other than inherited DNA. Preeclampsia is polygenic, involving many small genetic contributions rather than one dominant mutation, and it is also deeply shaped by conditions in each individual pregnancy.

Specific Genes That Have Been Identified

The search for particular genetic culprits has accelerated in recent years thanks to large-scale genome-wide association studies. A 2023 study published in JAMA Cardiology pooled data from multiple populations and identified nine spots in the genome that reached statistical significance for preeclampsia, with an additional four loci linked to broader hypertensive disorders of pregnancy. A multi-ancestry study added two more maternal loci, including variants near the RARB gene on chromosome 3, each roughly tripling the odds of hypertensive disorders in carriers.

None of these individual variants, on their own, account for a large share of preeclampsia cases. Each adds a small nudge in risk. The picture that is emerging looks a lot like the genetics of heart disease or type 2 diabetes: dozens or hundreds of variants, each contributing modestly, with environmental and pregnancy-specific factors determining whether the accumulated genetic risk actually tips someone over the threshold.

The Father’s Genes and the Fetal Genome

Preeclampsia is unusual among pregnancy complications in that the father’s genetics matter, too. The placenta carries both maternal and paternal DNA, and evidence suggests that immune incompatibility between maternal and paternal genes plays a meaningful role. A Norwegian study found that men who were themselves born from preeclamptic pregnancies were about twice as likely to father a pregnancy complicated by preeclampsia, even though they obviously do not carry the pregnancy themselves. An analysis of Swedish pregnancies estimated that paternal factors account for about 13% of preeclampsia risk, likely through genetic interactions with the mother’s immune system.

Perhaps the most striking genetic finding related to the fetal genome involves the FLT1 gene on chromosome 13. A genome-wide scan of babies born from preeclamptic pregnancies identified variants near FLT1 as the first genome-wide significant susceptibility locus for the condition. FLT1 encodes a protein whose placental form, called sFlt-1, is directly involved in the blood vessel dysfunction that drives preeclampsia symptoms. When the fetal-placental tissue overproduces sFlt-1, it starves the mother’s blood vessels of growth signals they need to function properly, leading to high blood pressure and organ stress. This is a case where the baby’s own genetic makeup, half of which comes from the father, can trigger a dangerous maternal condition.

What Goes Wrong in the Placenta

Genetics set the stage, but the actual disease unfolds in the placenta and the blood vessels that feed it. In a healthy pregnancy, specialized cells from the placenta remodel the spiral arteries in the uterine wall, widening them to deliver a generous blood supply to the growing fetus. In preeclampsia, this remodeling fails. The arteries remain narrow and stiff, reducing blood flow to the placenta.

The oxygen-starved placenta then floods the mother’s bloodstream with stress signals, including excess sFlt-1, which disrupts the lining of blood vessels throughout the body. This produces the hallmark signs of preeclampsia: high blood pressure, protein spilling into the urine, and in severe cases, damage to the liver, kidneys, or brain. The ratio of sFlt-1 to a pro-growth protein called PlGF has become a useful clinical marker. When sFlt-1 is high and PlGF is low, it signals the kind of angiogenic imbalance characteristic of preeclampsia.

Immune processes amplify the problem. Successful pregnancy requires the mother’s immune system to tolerate a fetus that is genetically half foreign. When that tolerance breaks down, excessive immune activation at the placenta and throughout the body worsens inflammation and vascular damage. Epigenetic changes, where genes are switched on or off without altering the DNA sequence itself, also appear to influence how placental cells invade the uterine wall and how fetal development proceeds under stress.

Early-Onset Versus Late-Onset Preeclampsia

Preeclampsia is not a single disease. It splits into at least two subtypes that differ in timing, mechanism, and likely genetic contribution. Early-onset preeclampsia appears before 34 weeks of pregnancy and is driven primarily by defective placentation, the failed spiral artery remodeling described above. It tends to be more severe, with higher rates of complications for both mother and baby.

Late-onset preeclampsia, appearing at or after 34 weeks, is more closely linked to the mother’s pre-existing cardiovascular and metabolic health. A study comparing gene expression in placentas from both subtypes found strikingly different molecular signatures: nearly 3,000 genes were dysregulated in early-onset cases and were concentrated in metabolic pathways, while late-onset cases showed a smaller set of about 375 altered genes focused on immune and autoimmune pathways. The practical upshot is that different women develop preeclampsia for somewhat different reasons, and the genetic contribution may be stronger in the early-onset form where placental dysfunction is the primary driver.

Non-Genetic Risk Factors That Interact With Genes

Genetics do not operate in a vacuum. Several well-established clinical risk factors can push someone who is genetically susceptible over the line into preeclampsia, or can trigger it even in someone without a strong family history.

Racial and Ethnic Disparities

Black and African American women face consistently higher rates of preeclampsia, along with worse outcomes when it occurs, compared with white women. American Indian and Alaska Native women are also disproportionately affected. Asian women, by contrast, tend to have lower preeclampsia rates, while data on Hispanic women are mixed.

It is tempting to chalk these disparities up to the higher baseline rates of obesity, diabetes, and chronic hypertension in some of these groups. Those conditions do disproportionately affect non-Hispanic Black, American Indian, and Hispanic populations. But the evidence shows that addressing those modifiable risk factors does not erase the disparity, suggesting that structural factors like chronic stress, unequal access to prenatal care, and neighborhood-level exposures also contribute. A nationwide analysis of preeclampsia hospitalizations in the United States from 2004 to 2019 found that Black women had higher in-hospital mortality across all income levels, and that high-income Black women still faced worse cardiovascular complication rates than low-income white women. This is a sobering finding that points to systemic inequities beyond individual health behaviors or genetic predisposition.

Screening in the First Trimester

Because preeclampsia develops gradually and its severity depends on how early it is caught, there has been a major push to predict it before symptoms appear. The most promising screening models combine a woman’s medical history with physical measurements and blood markers taken in the first trimester. One approach that includes blood pressure, uterine artery blood flow measurements, and levels of PlGF and sFlt-1 can detect roughly 88% of women who will go on to develop early-onset preeclampsia, at a 5% false-positive rate. Detection of late-onset preeclampsia with the same approach is less impressive, catching about two-thirds of cases, reflecting the different biology of the late form.

Simpler models using only maternal characteristics and uterine artery Doppler with PlGF can predict about half of early-onset cases. Performance improves when more markers are layered in, but access to those markers varies by clinic and country. The practical value of first-trimester screening is that it identifies women who benefit most from preventive treatment, particularly low-dose aspirin.

What Can Be Done to Reduce the Risk

For women identified as high-risk, low-dose aspirin started early in pregnancy is the most established preventive intervention. The landmark ASPRE trial found that aspirin at 150 mg per day, started before 16 weeks of pregnancy and taken at bedtime, cut the rate of preterm preeclampsia by about 62% in a population identified through first-trimester combined screening. Aspirin works by suppressing a pro-clotting molecule called thromboxane while preserving protective blood vessel signals, which helps counteract the vascular imbalance that characterizes preeclampsia.

Aspirin does not work for everyone, and its benefit is strongest for preterm preeclampsia, with weaker evidence for preventing the late-onset form. Researchers have been exploring other options, including pravastatin, metformin, and even experimental molecular therapies designed to directly lower circulating sFlt-1 levels or silence the genes that overproduce it. Some case series have attempted to physically remove excess sFlt-1 from the blood to stabilize severe cases and buy time before delivery. None of these approaches are yet standard of care, but they illustrate how the growing understanding of preeclampsia’s molecular machinery is opening doors that were closed a decade ago.

Long-Term Cardiovascular Consequences

Preeclampsia does not simply end with delivery. Women who have had preeclampsia face elevated cardiovascular risk for decades afterward. A large Korean cohort study with over 20 years of follow-up found that women with a history of preeclampsia had about 66% higher odds of ischemic heart disease and about 48% higher odds of stroke compared with women whose pregnancies were uncomplicated. A pooled analysis across multiple studies put the numbers in a similar range. Women with severe or recurrent preeclampsia face especially elevated risks, and many develop chronic hypertension within a decade after delivery.

The shared mechanisms between preeclampsia and later heart disease include endothelial dysfunction and chronic inflammation. There is an ongoing debate about whether preeclampsia directly damages the cardiovascular system or whether it reveals a pre-existing vulnerability that was going to surface eventually. The answer is probably both: women genetically predisposed to vascular problems are more likely to develop preeclampsia, and the metabolic stress of preeclampsia itself accelerates vascular aging.

Effects on the Children

The children born from preeclamptic pregnancies also carry lasting health effects. A population-based cohort study found that children born at full term who had been exposed to preeclampsia in the womb had a roughly 60% higher rate of hospitalization for endocrine, nutritional, and metabolic diseases and about 50% higher rates of blood-related disorders compared with unexposed children. Daughters of preeclamptic mothers are themselves at elevated risk for preeclampsia and cardiovascular disease later in life, continuing the intergenerational cycle.

This intergenerational pattern could reflect shared genetics, shared environment, or epigenetic changes imprinted during fetal development. It is likely all three. The practical implication is that a woman whose mother had preeclampsia should mention it to her prenatal care provider, and the children born from preeclamptic pregnancies may benefit from earlier and more attentive cardiovascular monitoring as they grow up.

Why Preeclampsia May Be Uniquely Human

One genuinely surprising aspect of preeclampsia is that it appears to be essentially unique to our species. Anthropological research has linked this to two features of human pregnancy that are extreme compared to other mammals: the fetal brain is enormously energy-demanding, requiring heavy blood flow through the placenta, and human placental cells invade the uterine wall far more aggressively than in most other species. This deep invasion is necessary to remodel the spiral arteries enough to feed that hungry brain. When the remodeling goes wrong, the consequences are severe precisely because the system was designed to push blood delivery to an extreme. In other words, preeclampsia may be an evolutionary side effect of having the largest, most metabolically expensive brains in the animal kingdom.

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