The genetic architecture of cervical length is shared with spontaneous preterm birth risk
Abstract Background Sonographic cervical length is a powerful predictor of maternal risk for spontaneous preterm birth (sPTB). Twin and family studies have established a maternal genetic heritability for sPTB ranging from 13 to 20%, however, there is no corresponding estimate for the heritability of...
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Nature Portfolio
2025-08-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-01078-0 |
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| author | Hope M. Wolf Bradley T. Webb Jerome F. Strauss Adi L. Tarca Roberto Romero Sonia S. Hassan Shawn J. Latendresse Tinnakorn Chaiworapongsa Stanley Berry Nardhy Gomez-Lopez Piya Chaemsaithong Timothy P. York |
| author_facet | Hope M. Wolf Bradley T. Webb Jerome F. Strauss Adi L. Tarca Roberto Romero Sonia S. Hassan Shawn J. Latendresse Tinnakorn Chaiworapongsa Stanley Berry Nardhy Gomez-Lopez Piya Chaemsaithong Timothy P. York |
| author_sort | Hope M. Wolf |
| collection | DOAJ |
| description | Abstract Background Sonographic cervical length is a powerful predictor of maternal risk for spontaneous preterm birth (sPTB). Twin and family studies have established a maternal genetic heritability for sPTB ranging from 13 to 20%, however, there is no corresponding estimate for the heritability of mid-trimester cervical length, or an understanding of how genetic factors contribute to cervical changes across pregnancy. Methods This study was based on a prospective longitudinal cohort of (N = 5,160) Black/African American women who underwent serial sonographic examination of the uterine cervix during pregnancy and were genotyped via next-generation low-pass whole genome sequencing. Results Bivariate genetic correlations estimated using genome-wide complex trait analysis (GCTA) indicated that a large proportion of the genes influencing cervical change across pregnancy also influenced gestational duration. SNP-level associations were observed near genes involved in the progesterone, estrogen, and insulin signaling pathways. Conclusions These results suggest that a large proportion of genetic loci for preterm birth exert their influence through the process of cervical remodeling. Polygenic profiling of maternal genetic liability to cervical shortening could aid in the development of clinical risk assessment tools to identify high-risk women who may benefit from more frequent cervical length screening and earlier interventions to prevent preterm delivery. |
| format | Article |
| id | doaj-art-ec5a8466b45d40d48fee45a0bb29ad76 |
| institution | Kabale University |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-08-01 |
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| spelling | doaj-art-ec5a8466b45d40d48fee45a0bb29ad762025-08-20T03:46:29ZengNature PortfolioCommunications Medicine2730-664X2025-08-015111110.1038/s43856-025-01078-0The genetic architecture of cervical length is shared with spontaneous preterm birth riskHope M. Wolf0Bradley T. Webb1Jerome F. Strauss2Adi L. Tarca3Roberto Romero4Sonia S. Hassan5Shawn J. Latendresse6Tinnakorn Chaiworapongsa7Stanley Berry8Nardhy Gomez-Lopez9Piya Chaemsaithong10Timothy P. York11Department of Human and Molecular Genetics, Virginia Commonwealth University School of MedicineGenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI InternationalDepartment of Obstetrics and Gynecology, Virginia Commonwealth University School of MedicinePerinatology Research Branch*, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, U.S. Department of Health and Human ServicesPerinatology Research Branch*, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, U.S. Department of Health and Human ServicesDepartment of Obstetrics and Gynecology, University of MichiganDepartment of Psychology and Neuroscience, Baylor UniversityDepartments of Obstetrics and Gynecology & Pathology and Immunology, Washington University School of MedicineDepartments of Obstetrics and Gynecology & Pathology and Immunology, Washington University School of MedicineDepartments of Obstetrics and Gynecology & Pathology and Immunology, Washington University School of MedicineDepartments of Obstetrics and Gynecology & Pathology and Immunology, Washington University School of MedicineDepartment of Human and Molecular Genetics, Virginia Commonwealth University School of MedicineAbstract Background Sonographic cervical length is a powerful predictor of maternal risk for spontaneous preterm birth (sPTB). Twin and family studies have established a maternal genetic heritability for sPTB ranging from 13 to 20%, however, there is no corresponding estimate for the heritability of mid-trimester cervical length, or an understanding of how genetic factors contribute to cervical changes across pregnancy. Methods This study was based on a prospective longitudinal cohort of (N = 5,160) Black/African American women who underwent serial sonographic examination of the uterine cervix during pregnancy and were genotyped via next-generation low-pass whole genome sequencing. Results Bivariate genetic correlations estimated using genome-wide complex trait analysis (GCTA) indicated that a large proportion of the genes influencing cervical change across pregnancy also influenced gestational duration. SNP-level associations were observed near genes involved in the progesterone, estrogen, and insulin signaling pathways. Conclusions These results suggest that a large proportion of genetic loci for preterm birth exert their influence through the process of cervical remodeling. Polygenic profiling of maternal genetic liability to cervical shortening could aid in the development of clinical risk assessment tools to identify high-risk women who may benefit from more frequent cervical length screening and earlier interventions to prevent preterm delivery.https://doi.org/10.1038/s43856-025-01078-0 |
| spellingShingle | Hope M. Wolf Bradley T. Webb Jerome F. Strauss Adi L. Tarca Roberto Romero Sonia S. Hassan Shawn J. Latendresse Tinnakorn Chaiworapongsa Stanley Berry Nardhy Gomez-Lopez Piya Chaemsaithong Timothy P. York The genetic architecture of cervical length is shared with spontaneous preterm birth risk Communications Medicine |
| title | The genetic architecture of cervical length is shared with spontaneous preterm birth risk |
| title_full | The genetic architecture of cervical length is shared with spontaneous preterm birth risk |
| title_fullStr | The genetic architecture of cervical length is shared with spontaneous preterm birth risk |
| title_full_unstemmed | The genetic architecture of cervical length is shared with spontaneous preterm birth risk |
| title_short | The genetic architecture of cervical length is shared with spontaneous preterm birth risk |
| title_sort | genetic architecture of cervical length is shared with spontaneous preterm birth risk |
| url | https://doi.org/10.1038/s43856-025-01078-0 |
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