Molecular subtyping of hypertensive disorders of pregnancy
Abstract Hypertensive disorders of pregnancy (HDP), including preeclampsia, affect 1 in 6 pregnancies, are major contributors to maternal morbidity and mortality, yet lack precision medicine strategies. Analyzing transcriptomic data from a prospectively-collected diverse cohort (n = 9102), this stud...
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58157-y |
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| author | Michal A. Elovitz Elaine P. S. Gee Nathaniel Delaney-Busch Alison B. Moe Mitsu Reddy Arkady Khodursky Johnny La Ilma Abbas Kay Mekaru Hunter Collins Farooq Siddiqui Rory Nolan Rupsa C. Boelig Daniel G. Kiefer Pamela M. Simmons George R. Saade Antonio Saad Ebony B. Carter Thomas F. McElrath Stephen R. Quake Mark A. DePristo Carrie Haverty Manfred Lee Eugeni Namsaraev Vincenzo Berghella Ai-ris Y. Collier Antonia I. Frolova Esther Park-Hwang Luis D. Pacheco Elizabeth F. Sutton Maneesh Jain Kara Rood William A. Grobman Joseph R. Biggio Cynthia Gyamfi-Bannerman Arun Jeyabalan Morten Rasmussen |
| author_facet | Michal A. Elovitz Elaine P. S. Gee Nathaniel Delaney-Busch Alison B. Moe Mitsu Reddy Arkady Khodursky Johnny La Ilma Abbas Kay Mekaru Hunter Collins Farooq Siddiqui Rory Nolan Rupsa C. Boelig Daniel G. Kiefer Pamela M. Simmons George R. Saade Antonio Saad Ebony B. Carter Thomas F. McElrath Stephen R. Quake Mark A. DePristo Carrie Haverty Manfred Lee Eugeni Namsaraev Vincenzo Berghella Ai-ris Y. Collier Antonia I. Frolova Esther Park-Hwang Luis D. Pacheco Elizabeth F. Sutton Maneesh Jain Kara Rood William A. Grobman Joseph R. Biggio Cynthia Gyamfi-Bannerman Arun Jeyabalan Morten Rasmussen |
| author_sort | Michal A. Elovitz |
| collection | DOAJ |
| description | Abstract Hypertensive disorders of pregnancy (HDP), including preeclampsia, affect 1 in 6 pregnancies, are major contributors to maternal morbidity and mortality, yet lack precision medicine strategies. Analyzing transcriptomic data from a prospectively-collected diverse cohort (n = 9102), this study reveals distinct RNA subtypes in maternal blood, reclassifying clinical HDP phenotypes like early/late-onset preeclampsia. The placental gene PAPPA2 strongly predicts the most severe forms of preeclampsia in individuals without pre-existing high risk factors, months before symptoms, and its overexpression correlates with earlier delivery in a dose-dependent manner. Further, molecular subtypes characterized by immune genes are upregulated in less severe forms of HDP. These results reclassify HDP clinical phenotypes into two distinct molecular subtypes, placental-associated or immune-associated. Validation performance for placental-associated HDP yields an AUC of 0.88 in the advanced maternal age population without pre-existing high risk factors. Molecular subtypes create new opportunities to apply precision-based medicine in maternal health. |
| format | Article |
| id | doaj-art-0f5e6ea813804849891f86fa595e0cf2 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0f5e6ea813804849891f86fa595e0cf22025-08-20T02:12:06ZengNature PortfolioNature Communications2041-17232025-04-0116111410.1038/s41467-025-58157-yMolecular subtyping of hypertensive disorders of pregnancyMichal A. Elovitz0Elaine P. S. Gee1Nathaniel Delaney-Busch2Alison B. Moe3Mitsu Reddy4Arkady Khodursky5Johnny La6Ilma Abbas7Kay Mekaru8Hunter Collins9Farooq Siddiqui10Rory Nolan11Rupsa C. Boelig12Daniel G. Kiefer13Pamela M. Simmons14George R. Saade15Antonio Saad16Ebony B. Carter17Thomas F. McElrath18Stephen R. Quake19Mark A. DePristo20Carrie Haverty21Manfred Lee22Eugeni Namsaraev23Vincenzo Berghella24Ai-ris Y. Collier25Antonia I. Frolova26Esther Park-Hwang27Luis D. Pacheco28Elizabeth F. Sutton29Maneesh Jain30Kara Rood31William A. Grobman32Joseph R. Biggio33Cynthia Gyamfi-Bannerman34Arun Jeyabalan35Morten Rasmussen36Mirvie Inc.Mirvie Inc.Mirvie Inc.Mirvie Inc.Mirvie Inc.Mirvie Inc.Mirvie Inc.Mirvie Inc.Mirvie Inc.Mirvie Inc.Mirvie Inc.Mirvie Inc.Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson UniversityWomen’s Care FloridaWoman’s HospitalEastern Virginia Medical SchoolInova HealthUniversity of North Carolina at Chapel HillMirvie Inc.Department of Bioengineering, Stanford UniversityBigHat Biosciences Inc.Mirvie Inc.Mirvie Inc.Mirvie Inc.Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Obstetrics and Gynecology, Beth Israel Deaconess Medical CenterWashington University School of MedicineMultiCare Health SystemUniverity of Texas Medical BranchWoman’s HospitalMirvie Inc.The Ohio State UniversityThe Ohio State UniversityOchsner HealthUniversity of California San DiegoUniversity of PittsburghMirvie Inc.Abstract Hypertensive disorders of pregnancy (HDP), including preeclampsia, affect 1 in 6 pregnancies, are major contributors to maternal morbidity and mortality, yet lack precision medicine strategies. Analyzing transcriptomic data from a prospectively-collected diverse cohort (n = 9102), this study reveals distinct RNA subtypes in maternal blood, reclassifying clinical HDP phenotypes like early/late-onset preeclampsia. The placental gene PAPPA2 strongly predicts the most severe forms of preeclampsia in individuals without pre-existing high risk factors, months before symptoms, and its overexpression correlates with earlier delivery in a dose-dependent manner. Further, molecular subtypes characterized by immune genes are upregulated in less severe forms of HDP. These results reclassify HDP clinical phenotypes into two distinct molecular subtypes, placental-associated or immune-associated. Validation performance for placental-associated HDP yields an AUC of 0.88 in the advanced maternal age population without pre-existing high risk factors. Molecular subtypes create new opportunities to apply precision-based medicine in maternal health.https://doi.org/10.1038/s41467-025-58157-y |
| spellingShingle | Michal A. Elovitz Elaine P. S. Gee Nathaniel Delaney-Busch Alison B. Moe Mitsu Reddy Arkady Khodursky Johnny La Ilma Abbas Kay Mekaru Hunter Collins Farooq Siddiqui Rory Nolan Rupsa C. Boelig Daniel G. Kiefer Pamela M. Simmons George R. Saade Antonio Saad Ebony B. Carter Thomas F. McElrath Stephen R. Quake Mark A. DePristo Carrie Haverty Manfred Lee Eugeni Namsaraev Vincenzo Berghella Ai-ris Y. Collier Antonia I. Frolova Esther Park-Hwang Luis D. Pacheco Elizabeth F. Sutton Maneesh Jain Kara Rood William A. Grobman Joseph R. Biggio Cynthia Gyamfi-Bannerman Arun Jeyabalan Morten Rasmussen Molecular subtyping of hypertensive disorders of pregnancy Nature Communications |
| title | Molecular subtyping of hypertensive disorders of pregnancy |
| title_full | Molecular subtyping of hypertensive disorders of pregnancy |
| title_fullStr | Molecular subtyping of hypertensive disorders of pregnancy |
| title_full_unstemmed | Molecular subtyping of hypertensive disorders of pregnancy |
| title_short | Molecular subtyping of hypertensive disorders of pregnancy |
| title_sort | molecular subtyping of hypertensive disorders of pregnancy |
| url | https://doi.org/10.1038/s41467-025-58157-y |
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