Is Preeclampsia Genetic? NPR3, MTHFR-CLCN6 and What a Polygenic Score Can Actually Tell You

Is Preeclampsia Genetic? NPR3, MTHFR-CLCN6 and What a Polygenic Score Can Actually Tell You

This article is for educational purposes only. It is not a substitute for advice from a licensed physician, board-certified medical geneticist, or board-certified genetic counselor. For any decisions about testing, treatment, or care, consult a qualified clinician. In emergencies, call 911.

Bottom line: Preeclampsia is polygenic, meaning many genes each add a little risk. There is no single gene to be positive or negative for. A 2023 multi-ancestry meta-analysis of 20,064 cases and 703,117 controls found 18 loci, or stretches of DNA linked to the condition. Adding its polygenic score moved the model’s C-statistic by only 0.011, a tiny gain. The C-statistic measures how well a model separates who will and will not develop a condition. A Swedish cohort of 701,488 pregnancies assigned 35% of liability variance to maternal genes and 20% to fetal genes. Read that as roughly a third of the tendency tracing to the mother’s genes. Preeclampsia complicates roughly 4% of US pregnancies. Even the top polygenic decile, the highest-scoring 10%, sat near 10% in two validation cohorts. No professional guideline currently uses a polygenic score to decide who gets low-dose aspirin.

What you’ll learn

• Why “is preeclampsia genetic?” has two answers, because two genomes contribute
• How to convert a percentile or a family history into an absolute percentage against the roughly 4% US baseline
• Why the MTHFR-CLCN6 locus name is not a reason to buy methylfolate, on four independent grounds
• What the FDA-authorized preeclampsia blood tests are actually indicated for, and what US and Canadian genetic-privacy law does and does not cover

Read this first: the warning signs that mean call today

Genetics is the slow half of this story. Symptom recognition is the fast half, and it applies to every pregnancy. Contact your obstetric provider the same day, or go to emergency care, if any of the following appear during pregnancy or in the weeks after delivery:

• A severe headache, or a headache that will not go away
• Any change in vision, such as blurring, flashing lights or spots
• Pain in the upper abdomen, typically under the ribs on the right side
• Sudden swelling of the face or hands
• Shortness of breath
• A noticeable drop in your baby’s movements
• A seizure, which is a medical emergency: call 911

The diagnostic criteria behind those features, including the definition of “preeclampsia with severe features,” are set out in ACOG Practice Bulletin No. 222. That is the document FDA’s authorized sFlt-1/PlGF indication points to for that definition. In Canada, SOGC Guideline No. 426 covers the same disorders. Reporting a symptom is not the same as diagnosing yourself, and the thresholds belong to the clinician who examines you.

Two points hold before any of the genetics below. First, these signs matter regardless of family history and regardless of any polygenic percentile, because preeclampsia complicates roughly 4% of US pregnancies overall. No consumer score rules it out, since a percentile places you in a population rather than predicting your pregnancy. Second, blood pressure is the measurement that catches most of this. CDC frames prevention around prompt identification and blood-pressure measurement throughout pregnancy, including self-monitoring.

Section recap: Severe headache, visual changes, upper-abdominal pain, sudden swelling, breathlessness, reduced fetal movement or a seizure all warrant urgent attention. Contact your obstetric provider the same day, or go to emergency care. These signs can occur with no family history and whatever a polygenic score says.

Preeclampsia is polygenic, so “is it genetic?” has two answers

Preeclampsia is a hypertensive disorder that appears during pregnancy. Many readers arrive expecting a yes-or-no gene result. Research has not identified a single causal variant, so no person is simply “positive” or “negative” for preeclampsia.

The clearest inheritance numbers come from Sweden. Researchers linked national birth and multi-generation registries covering 701,488 pregnancies and 244,564 sibling pairs. They then split the variance in liability, meaning the underlying tendency toward the condition, into components.

Component	Share of variance in liability
Maternal genetic effects	35%
Fetal genetic effects	20%
Couple effect	13%
Shared sibling environment	under 1%
Unmeasured factors	32%

Roughly half of the liability is genetic, split across the pregnant person and the fetus. Maternal and paternal contributions to the fetal share were similar. This is exactly why your own risk and your daughter’s risk are related numbers, not the same number.

The fetal side has a named locus. The InterPregGen study ran the first genome-wide scan of offspring from preeclamptic pregnancies, with 4,380 cases and 310,238 controls. It found rs4769613 near FLT1, the gene encoding Fms-like tyrosine kinase 1. The placental form of that protein is soluble sFlt-1, an anti-angiogenic factor, meaning a molecule that suppresses blood-vessel growth. It returns later as the analyte in an FDA-authorized blood test.

The maternal side was mapped in detail in 2023. A multi-ancestry meta-analysis pooled 20,064 preeclampsia or eclampsia cases against 703,117 controls. It also pooled 11,027 gestational-hypertension cases against 412,788 controls. The analysis reported 18 independent loci, 12 of them new, including MTHFR-CLCN6, WNT3A, NPR3, PGR and RGL3. The authors grouped the biology into five themes:

• Natriuretic peptide signaling, a hormone system that helps regulate blood pressure and fluid balance
• Angiogenesis, the growth of new blood vessels
• Renal glomerular function, the filtering units of the kidney
• Trophoblast development, the cells that build the placenta
• Immune dysregulation

Some of that biology is shared with ordinary blood pressure. A separate meta-analysis in European and Central Asian mothers found preeclampsia signals at ZNF831 and FTO, both established blood-pressure loci. Known blood-pressure variants at MECOM, FGF5 and SH2B3 also associated with preeclampsia through the maternal genome. A polygenic score built for hypertension associated with preeclampsia as well.

Think of it as a scale loaded with many small weights rather than one heavy stone. Removing any single weight barely moves the pan. That is the practical meaning of “polygenic,” and it is worth saying out loud at a preconception or early prenatal visit so your clinician knows what prompted the question.

Section recap: Preeclampsia has no single causal gene. Swedish registry data assign 35% of liability variance to maternal genes and 20% to fetal genes, and the 2023 meta-analysis maps 18 maternal loci across five biological themes.

What the 23andMe preeclampsia report actually is, and the regulatory line it sits on

If a consumer report is what brought you here, the exact product matters. On the 23andMe clinician-facing report list, health predispositions are split into two groups. One group holds reports that meet FDA requirements for genetic health risks. The other holds reports “Powered by 23andMe Research.” Preeclampsia sits in the polygenic table of that second group.

23andMe states the report is built on 14,000-plus contributing variants. It lists relevance for East and Southeast Asian, European, Hispanic or Latino, Northern African or Western Asian, South Asian, and Sub-Saharan African or African American groups.

The company’s own footnote is the sentence to read twice. It says the second kind consists of “reports which are based on 23andMe research and have not been reviewed by the FDA”. These reports, it adds, “are not intended to tell a person anything about his or her current state of health, or to be used to make medical decisions”.

That vendor statement can be checked against the regulator’s own database. A live query of the FDA device submission records for applicant 23andMe returns exactly nine authorizations. They cover the Personal Genome Service, hereditary thrombophilia, BRCA1 and BRCA2 variants, pharmacogenetic reports, MUTYH-associated polyposis and HOXB13-related prostate cancer risk. None of them is a preeclampsia report. The accurate phrasing is that FDA’s device database records no marketing authorization for a 23andMe preeclampsia report. It is not the same as saying the agency reviewed and rejected one.

Two further limits apply to any polygenic score, not just this one.

• A percentile is a population statement. A polygenic score adds up many small allelic effects to place a person within a reference group. A task force convened by the International Common Disease Alliance named the misunderstanding and misuse of these scores as a leading risk of clinical use. It also identified gaps in best practices, risk communication and regulatory frameworks that remain unresolved.
• Accuracy is uneven across ancestries. The 2023 discovery sample was 78.0% European, 21.2% Asian, 0.5% admixed American and 0.3% African. The authors state plainly that score performance “was better in female participants with European versus other ancestries”.

A credit score built mostly on one country’s borrowers will misprice applicants elsewhere, even when the underlying math is sound. The number is real; its calibration is not universal. Bring the screenshot to your obstetric provider or primary care clinician anyway, because it is a reasonable prompt for an earlier risk conversation.

Section recap: The preeclampsia report is a research-grade polygenic score that 23andMe itself says has not been FDA-reviewed, and the FDA device database records no authorization for it. Treat the percentile as a population placement, not a personal prognosis.

Turning a percentile into an absolute number you can reason about

“Increased risk” is unusable until it is multiplied into a baseline. Start with the correct denominator. The US Preventive Services Task Force states that preeclampsia “is a complication in approximately 4% of pregnancies in the US”. Preeclampsia also accounts for 6% of preterm births and 19% of medically indicated preterm births.

One widely quoted CDC figure is not that number. CDC’s analysis of the National Inpatient Sample found that hypertensive disorders in pregnancy rose from 13.3% of delivery hospitalizations in 2017 to 15.9% in 2019. That range bundles chronic hypertension and gestational hypertension together with preeclampsia. It is not the preeclampsia rate, and it must not be used as the baseline a relative risk multiplies into. The same CDC analysis reported that 31.6% of deaths during delivery hospitalization carried a hypertensive-disorder diagnosis code.

Now the multipliers. A systematic review of studies at antenatal booking reported unadjusted relative risks for factors known before pregnancy. A second review of 92 cohort studies covering 25,356,688 pregnancies reported pooled absolute rates alongside relative risks.

Factor	Pooled rate of preeclampsia	Relative risk
Antiphospholipid antibody syndrome	17.3%	9.72
Chronic hypertension	16.0%	5.1
Prior preeclampsia	not reported	8.4, 7.19
Pregestational diabetes	11.0%	3.7
Prepregnancy BMI over 30	7.1%	2.8
Assisted reproductive technology	6.2%	1.8
Family history (mother or sister)	not reported	2.90
First pregnancy (nulliparity)	not reported	2.91

Family history of preeclampsia carries an unadjusted relative risk of 2.90, with a confidence interval, or plausible range, of 1.70 to 4.93. Applied to a roughly 4% baseline, that lands somewhere near 10% to 12%. Roughly nine in ten such pregnancies still do not develop preeclampsia.

The polygenic data land in the same neighbourhood. In two external validation cohorts, prevalence ran from about 4% in the bottom decile of the score to about 10% in the top decile. That pattern held in HUNT, with 25,582 Norwegian women, and in the US nuMoM2b cohort, with 6,225 first-time mothers. Comparing the top 10% against everyone else gave an odds ratio of 1.85 in HUNT and 1.78 in nuMoM2b. An odds ratio compares the odds of an outcome between two groups. Adjusting for first-trimester systolic blood pressure, antihypertensive use and body mass index pulled the second figure down to 1.64.

Two caveats belong with those numbers. First, adding the polygenic score moved the model’s C-statistic only from 0.690 to 0.701. That is a small gain in discrimination. Second, every figure here is a cohort average, not your personal odds. Even the highest-ranking clinical risk factor tops out near one in six, not a certainty. A clinician who knows your blood pressure, your history and your current pregnancy can place you far better than a table can.

Section recap: Multiply relative risks into the roughly 4% US preeclampsia baseline, never into the 15.9% figure for all hypertensive disorders. Family history and the top polygenic decile both point to a band around 10%, which leaves most pregnancies unaffected.

The MTHFR trap: why MTHFR-CLCN6 is not permission to buy methylfolate

Of the 12 new loci, one name will pull readers straight into supplement marketing. MTHFR is the most misused string in consumer genetics. There are four separate reasons not to act on it here, and dismissing any one of them still leaves three standing.

1. Locus labels name a neighbourhood, not a culprit. The 2023 paper lists its loci under a column headed literally “Nearest gene”. The canonical demonstration is FTO. Obesity-associated variants sit inside FTO introns, and the locus is named after it. Yet those variants physically loop, across megabase distances, to the promoter of IRX3. In human brains the variants associate with IRX3 expression, not with FTO expression.
2. This paper’s own analysis points elsewhere. The lead variant at the MTHFR-CLCN6 locus is rs149764880, with an odds ratio of 1.12. The authors report that it colocalized with CLCN6 expression signals and with expression of NPPA, the gene encoding the precursor of atrial natriuretic peptide. Colocalized means one shared genetic signal appears to drive both the disease association and the gene’s activity. Their gene-prioritization method named NPPA as the most likely causal gene at that locus. MTHFR appears nowhere in the causal-gene prioritization, and folate metabolism is not among the five implicated themes.
3. A professional society already recommends against the test. The American College of Medical Genetics and Genomics (ACMG) addressed the test directly. Its guideline concluded: “There is growing evidence that MTHFR polymorphism testing has minimal clinical utility and, therefore should not be ordered as a part of a routine evaluation for thrombophilia”. That guideline addresses thrombophilia and recurrent pregnancy loss workups, not preeclampsia specifically, and it should not be stretched further.
4. High-dose folate was tested for preeclampsia and failed. The FACT trial randomized 2,464 pregnant women with at least one high-risk factor across 70 centres in five countries. The intervention was 4.0 mg of folic acid daily from 8 weeks until delivery, which is roughly ten times the standard preconception dose. Preeclampsia occurred in 14.8% of the folic acid group and 13.5% of the placebo group, a relative risk of 1.10. The trial concluded that supplementation beyond the first trimester “does not prevent pre-eclampsia in women at high risk”.

Standard folic acid still matters, for a different endpoint. USPSTF gives a Grade A recommendation that all persons planning or able to become pregnant take 0.4 to 0.8 mg of folic acid daily. The purpose is preventing neural tube defects, which affect an estimated 3,000 US pregnancies each year. Preeclampsia is not an outcome in that recommendation.

Buying methylfolate off a locus label is like renaming your street after the nearest landmark and then mailing your rent there. Ask a clinician or a genetic counselor before adding any supplement in pregnancy.

Section recap: The MTHFR-CLCN6 label names a genomic neighbourhood, and the likely causal gene there is NPPA. ACMG recommends against MTHFR polymorphism testing, and 4 mg daily folic acid did not prevent preeclampsia in a randomized trial.

What actually changes care today: low-dose aspirin, and who qualifies

One intervention has moved from research into routine practice, and it is not genomic. The USPSTF recommends “the use of low-dose aspirin (81 mg/d) as preventive medication for preeclampsia after 12 weeks of gestation in persons who are at high risk for preeclampsia”. That is a Grade B recommendation, published on 28 September 2021 and resting on 18 randomized trials covering 15,908 participants.

Eligibility is scored against the two-tier checklist in USPSTF Table 1.

Tier	Factors
High risk (one is enough)	Prior preeclampsia, especially with an adverse outcome; multifetal gestation; chronic hypertension; pregestational type 1 or type 2 diabetes; kidney disease; autoimmune disease such as lupus or antiphospholipid syndrome
Moderate risk (two or more may benefit)	First pregnancy; prepregnancy BMI over 30; family history of preeclampsia in a mother or sister; Black patients, due to social rather than biological factors; lower income; age 35 or older; prior low-birth-weight or small-for-gestational-age infant; prior adverse pregnancy outcome; pregnancy interval over 10 years; in vitro conception
Low risk	Previous uncomplicated full-term delivery; aspirin not recommended

USPSTF notes that preeclampsia incidence “would likely be at least 8%” among people carrying one high-risk factor. It also attributes the elevated risk among Black patients to environmental, social and historical inequities rather than biological propensity.

Read the moderate-risk row carefully if preeclampsia runs in your family and you have not given birth before. Family history in a mother or sister is on that list, and so is first pregnancy. USPSTF states that people with two or more moderate-risk factors may also benefit from low-dose aspirin. Your polygenic percentile appears nowhere on the table. Your family history already does, and it costs nothing to report.

The size of the benefit depends on who is treated.

• Screened high-risk population. The ASPRE trial randomized 1,776 singleton pregnancies to 150 mg of aspirin nightly or placebo, from 11 to 14 weeks until 36 weeks. Preterm preeclampsia occurred in 1.6% on aspirin versus 4.3% on placebo, an odds ratio of 0.38. Note the dose. ASPRE used 150 mg, not the 81 mg the USPSTF recommends.
• Everyone pooled. A Cochrane review of 77 trials and 40,249 women found antiplatelet agents reduced proteinuric preeclampsia by 18%. That is a relative risk of 0.82 and a number needed to treat of 61, or roughly 16 fewer cases per 1,000 women treated.
• Harms, stated honestly. Postpartum haemorrhage over 500 mL was probably slightly increased, at a relative risk of 1.06. Placental abruption was marginally increased, at 1.21, with a confidence interval crossing no effect.

ACOG Practice Bulletin 222 is the US reference for diagnosis and management of gestational hypertension and preeclampsia. In Canada, SOGC Guideline No. 426 covers diagnosis, prediction, prevention and postpartum care after a hypertensive disorder of pregnancy. Its intended users are explicitly all providers who care for women before, during or after pregnancy, so a Canadian reader can name it at an appointment. Dose and timing figures in this section come from USPSTF, not from SOGC.

None of this is a self-start decision. FDA has warned that NSAIDs used from around 20 weeks may cause rare but serious fetal kidney problems with low amniotic fluid. Aspirin at 81 mg is an exception only “under the direction of a health care clinician”. The 2023 meta-analysis did show that adding the top polygenic decile to the USPSTF major criteria raised sensitivity from 17.5% to 30.4%. No professional society has adopted that approach, and the analysis behind it is a reclassification exercise rather than a randomized trial.

Section recap: Low-dose aspirin at 81 mg daily after 12 weeks is the one guideline-backed action, scored against the USPSTF two-tier checklist where family history and first pregnancy already count. A polygenic score is not on that checklist, and aspirin remains a prescribing decision.

The blood tests regulators have authorized, and what they are not for

If 2023 news coverage left you believing a preeclampsia blood test can be requested early in pregnancy, the authorization says something narrower.

FDA granted De Novo request DEN220027 on 18 May 2023, to BRAHMS GmbH, part of Thermo Fisher Scientific, for the B.R.A.H.M.S sFlt-1/PlGF KRYPTOR Test System. The decision created regulation 21 CFR 862.1602 and product code QWH, a class II clinical chemistry category. Roche’s Elecsys sFlt-1 and Elecsys PlGF were cleared as 510(k) K241453 on 7 February 2025. Those are two different routes. A De Novo request creates a new device category when nothing equivalent already exists. A 510(k) clears a later device by showing it is substantially equivalent to one already on the market.

The authorized indication is specific. The two assays together aid risk assessment in “pregnant women (singleton pregnancies between gestational age 23+0 to 34+6/7 weeks) hospitalized for hypertensive disorders of pregnancy”. The stated purpose is assessing “progression to preeclampsia with severe features… within 2 weeks of presentation”. Three limits follow directly from that sentence.

• The patient is hospitalized, not attending a routine prenatal visit.
• She already has a hypertensive disorder of pregnancy.
• The window is 23+0 to 34+6/7 weeks, and the pregnancy is singleton.

The codified classification is blunter still. It states that this device type “is not intended for diagnosis of any disease”. Labeling must carry the statement that the result “is intended as an aid in the management of the patient, and not to be used to replace clinical judgement”. Both assays are prescription-use only and must be run together on the same sample.

The supporting study defines the same boundary. PRAECIS enrolled across 18 US centres and evaluated 1,014 hospitalized women between 23 and 35 weeks with a hypertensive disorder. A ratio of 40 or above gave a 65% positive predictive value and a 96% negative predictive value for progression to preeclampsia with severe features. That is roughly 65 of every 100 women above the threshold progressing, and 96 of every 100 below it not progressing.

Two more figures complete the picture. The area under the curve, a score running from 0.5 for a coin flip to 1.0 for a perfect test, was 0.92. Standard-of-care tests scored below 0.75. Women above the threshold had adverse maternal outcomes 16.1% of the time versus 2.8% below it. One disclosure belongs alongside those numbers: the study was funded by Cedars-Sinai Medical Center and Thermo Fisher Scientific, the manufacturer of the authorized device.

The analyte sFlt-1 is the placental form of the protein encoded by FLT1, the same gene flagged in the fetal genome scan. Genetics and diagnostics are pointing at one pathway from two directions.

Canadian availability is a separate question. Medical devices sold in Canada are licensed by Health Canada, and the Canadian licensing status of these two assays was not verified for this article. US authorization does not by itself make a test available in Canada, so check locally or provincially with your own provider rather than assuming. Think of the test as a smoke alarm inside a building that is already warm, not a fire-risk survey of the whole street. Whether it belongs in your care is a decision for the clinician managing the admission.

Section recap: The sFlt-1/PlGF tests are FDA-authorized prognostic tools for hospitalized patients with an existing hypertensive disorder between 23+0 and 34+6/7 weeks. They are not first-trimester screening tests, and the classification states they are not for diagnosis.

What it means for sisters, daughters, and your own next thirty years

Families often ask about cascade testing, where relatives are tested for the same variant found in one person. That pathway does not exist here. There is no single causal variant to test relatives for, and the contribution is split across two genomes anyway.

What does transfer is the family history itself, and it is already recognized. Family history of preeclampsia in a mother or sister sits on the USPSTF moderate-risk list. The unadjusted relative risk attached to it is 2.90. So the useful action costs nothing: a sister or daughter tells her own obstetric provider about the family pattern, early.

One finding changes the timescale of the whole question. A meta-analysis of 22 studies covering more than 6.4 million women, including more than 258,000 with preeclampsia, examined later cardiovascular outcomes.

Later outcome after preeclampsia	Risk ratio
Heart failure	4.19
Coronary heart disease	2.50
Cardiovascular death	2.21
Stroke	1.81

Those associations persisted after adjustment for age, body mass index and diabetes. The authors called for lifelong monitoring of cardiovascular risk factors in women with a preeclampsia history. That is consistent with the genetics. A hypertension polygenic score associates with preeclampsia, and the 2023 preeclampsia score also associated with hypertension in men, at an odds ratio of 1.12 per standard deviation.

The American Heart Association turned this into guidance. Its scientific statement holds that a history of adverse pregnancy outcomes “is a prompt for more vigorous primordial prevention of CVD risk factors and primary prevention of CVD”. It names diet and physical activity starting in the postpartum period and continuing across the lifespan. It is candid that the value of these outcomes in formally reclassifying risk may not be established. It also reports that Black and Asian women experience a higher proportion of adverse pregnancy outcomes, with more severe presentations. The statement proposes building a “fourth trimester” concept into policy and improving care transitions.

Practical takeaways that require no test:

• Attend postpartum blood-pressure follow-up, which SOGC Guideline No. 426 explicitly covers
• Tell every future primary care clinician about any hypertensive pregnancy
• Encourage sisters and daughters to report the family history at their own first prenatal visit

A preeclampsia history is less like a closed chapter and more like a permanent line in your medical chart. Ask your primary care clinician to record it.

Section recap: Cascade testing does not apply to a polygenic condition, but family history is already a recognized risk factor and is free to disclose. A preeclampsia history also carries a four-fold later heart-failure risk ratio, which makes postpartum and lifelong follow-up worthwhile.

Privacy, insurance, and who to actually talk to in the US and Canada

Genetic-privacy protection is real in both countries, and it is not identical.

In the US, the Genetic Information Nondiscrimination Act was enacted on 21 May 2008 as Public Law 110-233. Title I covers health insurance and Title II covers employment. The health-insurance rules took effect on 7 December 2009 and the employment rules on 10 January 2011.

The gap matters more than the dates. The National Human Genome Research Institute states it plainly: GINA’s protections “do not cover long-term care insurance, life insurance, or disability insurance,” though some states add their own protections. Two further exclusions apply. GINA does not reach employers with fewer than 15 employees, and the US military may use genetic information in employment decisions.

In Canada, the Genetic Non-Discrimination Act was assented to on 4 May 2017. Section 3(1) prohibits requiring anyone to undergo a genetic test as a condition of “providing goods or services,” entering or continuing a contract, or offering specific contract terms. Section 4(1) prohibits requiring disclosure of a test result on the same conditions. The Act was challenged as beyond Parliament’s criminal law power. The Supreme Court of Canada allowed the appeal on 10 July 2020 and upheld the Act, with four judges dissenting.

Question	United States	Canada
Health insurance	Covered by GINA Title I	Covered by the general prohibition
Employment	Covered by GINA Title II, employers with 15 or more staff	Covered by the general prohibition
Life, disability, long-term care insurance	Not covered by GINA; some state laws add protection	Reached by the broader “goods or services” wording
Legal form	Federal statute, 2008	Federal statute, 2017, upheld by the Supreme Court in 2020

A consumer research-report result is still genetic information, and the US gap sits precisely on the products people of childbearing age tend to buy. What a testing company does with your data is a separate question. Research-consent settings live in your account and are governed by contract, not insurance law.

Cost is the last practical barrier. HealthCare.gov lists preeclampsia prevention and screening for pregnant women with high blood pressure among its covered preventive services. Aspirin for preeclampsia prevention carries a USPSTF Grade B recommendation, and Grade B preventive services generally carry no cost sharing with an in-network provider. Coverage can still vary, and $0 is not guaranteed in every case.

On who to see: for interpretation of a genetic report, a board-certified genetic counselor can be located through the NSGC Find a Genetic Counselor directory. For polygenic pregnancy risk specifically, the more useful appointment is usually a preconception or early prenatal visit, with referral to maternal-fetal medicine if clinical risk factors stack up.

Section recap: GINA covers US health insurance and employment, but it leaves life, disability and long-term care insurance exposed. Canada’s statute reaches any goods or services and survived Supreme Court review in 2020. For a polygenic report, an early prenatal visit usually beats a testing appointment.

Frequently asked questions

Will I get preeclampsia?

Nobody can tell you that from a genetic result. Preeclampsia complicates roughly 4% of US pregnancies. A family history multiplies that by about 2.9 in unadjusted data, landing near 10% to 12%. The top polygenic decile sat near 10% in two validation cohorts. Most pregnancies in every one of those groups proceed without preeclampsia. Your clinician can refine this with your blood pressure and history.

Will my children inherit it?

Not in the way a single-gene condition is inherited. Swedish registry data assign 35% of liability variance to maternal genes and 20% to fetal genes. Because part of the contribution runs through the fetal genome, it comes partly from the father. There is no variant to test a daughter for, so the transferable information is the family history, which she should mention to her own obstetric provider.

Will this affect my health or life insurance?

In the US, GINA blocks health insurers from using genetic information, but it does not cover life, disability or long-term care insurance. Some states add protections. In Canada, the prohibition extends to any goods, services or contract, and the Supreme Court upheld it in 2020. Ask a genetic counselor or an independent adviser before applying for underwritten products.

Can my employer find out?

GINA Title II prohibits employers with 15 or more employees from using genetic information in employment decisions. Employers below that threshold are outside GINA, and the US military is permitted to use genetic information in employment decisions. In Canada, no person may require a test or its results as a condition of a contract or agreement. Report any concern to a qualified adviser rather than acting alone.

Should I get a second opinion?

Yes, if a report is driving a decision. A research-grade polygenic report is not a diagnosis, and the vendor states it should not be used to make medical decisions. The FDA device database records no marketing authorization for such a report. Bring it to a preconception or early prenatal visit, and ask about the USPSTF moderate-risk factor count rather than the percentile.

Summary

Preeclampsia genetics is real research that has not yet become a clinical instruction. The 2023 multi-ancestry meta-analysis mapped 18 loci across natriuretic peptide signaling, angiogenesis, kidney function, placental development and immunity. Swedish registry data show the liability is split across the maternal and fetal genomes. Blood-pressure genetics overlaps with it. A fetal-genome signal near FLT1 links the inheritance story to the sFlt-1 protein measured by FDA-authorized tests.

What that adds up to for a reader holding a consumer report is modest but not nothing.

• The percentile is a population placement whose calibration varies by ancestry
• It is not on any eligibility checklist, while your family history already is
• Low-dose aspirin at 81 mg after 12 weeks is the one guideline-backed preventive step, decided by a clinician against the USPSTF two-tier list
• The MTHFR-CLCN6 locus is not a reason to buy supplements, on four independent grounds
• A hypertensive pregnancy is a long-term cardiovascular signal worth carrying into every future appointment

None of that outranks the first section. Severe or persistent headache, changed vision, upper-abdominal pain, sudden swelling, breathlessness, reduced fetal movement or a seizure warrant same-day contact or emergency care, as set out in the first section of this article. Those signs can appear with no family history and whatever your score says.

This article is for educational purposes only. It is not a substitute for advice from a licensed physician, board-certified medical geneticist, or board-certified genetic counselor. For any decisions about testing, treatment, or care, consult a qualified clinician. In emergencies, call 911.

References

1. Honigberg MC, Truong B, Khan RR, et al. Polygenic prediction of preeclampsia and gestational hypertension. Nature Medicine. 2023;29(6):1540-1549. https://pubmed.ncbi.nlm.nih.gov/37248299/
2. Cnattingius S, Reilly M, Pawitan Y, Lichtenstein P. Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: a population-based Swedish cohort study. American Journal of Medical Genetics Part A. 2004;130A(4):365-371. https://pubmed.ncbi.nlm.nih.gov/15384082/
3. McGinnis R, Steinthorsdottir V, Williams NO, et al. Variants in the fetal genome near FLT1 are associated with risk of preeclampsia. Nature Genetics. 2017;49(8):1255-1260. https://pubmed.ncbi.nlm.nih.gov/28628106/
4. Steinthorsdottir V, McGinnis R, Williams NO, et al. Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women. Nature Communications. 2020;11:5976. https://pubmed.ncbi.nlm.nih.gov/33239696/
5. Ford ND, Cox S, Ko JY, et al. Hypertensive Disorders in Pregnancy and Mortality at Delivery Hospitalization – United States, 2017-2019. MMWR. 2022;71(17):585-591. https://www.cdc.gov/mmwr/volumes/71/wr/mm7117a1.htm
6. Rolnik DL, Wright D, Poon LC, et al. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia (ASPRE). New England Journal of Medicine. 2017;377(7):613-622. https://pubmed.ncbi.nlm.nih.gov/28657417/
7. Thadhani R, Lemoine E, Rana S, Costantine MM, et al. Circulating Angiogenic Factor Levels in Hypertensive Disorders of Pregnancy (PRAECIS). NEJM Evidence. 2022;1(12):EVIDoa2200161. https://pubmed.ncbi.nlm.nih.gov/38319832/
8. US Food and Drug Administration. De Novo DEN220027, B.R.A.H.M.S sFlt-1/PlGF KRYPTOR Test System, granted 2023-05-18; 510(k) K241453, Elecsys sFlt-1 and Elecsys PlGF, cleared 2025-02-07; product code QWH, 21 CFR 862.1602. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN220027
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Last updated: 2026-09-03

Author: Yu Mizuno (Editor-in-Chief, non-physician), GeneLumen editorial team. This article aggregates 25 sources (tier 1=14 / tier 2=10 / tier 3=1). Twenty-four come from peer-reviewed medical literature, regulators, statutes and public health agencies. One is a manufacturer document, cited as a vendor statement. Sources include the CDC, the FDA, the NIH National Human Genome Research Institute, the US Preventive Services Task Force, ACMG, ACOG and SOGC guidelines, and PubMed-indexed publications.

This article is for educational purposes only and is not a substitute for medical advice from a licensed physician, board-certified medical geneticist, or board-certified genetic counselor. In emergencies, call 911 (US/Canada).

Related: Genetic Diseases category

🇯🇵 For readers in Japan — a separate Japanese edition written for Japan’s healthcare system (not a translation): https://genelumen.com/ja/ja-genetic-diseases/preeclampsia-polygenic-risk-kazokureki-japan