Genetic predictors of blood pressure traits are associated with preeclampsia

Elizabeth A. Jasper; Jacklyn N. Hellwege; Joseph H. Breeyear; Brenda Xiao; Gail P. Jarvik; Ian B. Stanaway; Kathleen A. Leppig; Geetha Chittoor; M. Geoffrey Hayes; Ozan Dikilitas; Iftikhar J. Kullo; Ingrid A. Holm; Shefali Setia Verma; Todd L. Edwards; Digna R. Velez Edwards

doi:10.1038/s41598-024-68469-6

Genetic predictors of blood pressure traits are associated with preeclampsia

Elizabeth A. Jasper, Jacklyn N. Hellwege, Joseph H. Breeyear, Brenda Xiao, Gail P. Jarvik, Ian B. Stanaway, Kathleen A. Leppig, Geetha Chittoor, M. Geoffrey Hayes, Ozan Dikilitas, Iftikhar J. Kullo, Ingrid A. Holm, Shefali Setia Verma, Todd L. Edwards, Digna R. Velez Edwards^*

^*Corresponding author for this work

Medicine, Endocrinology Division

Research output: Contribution to journal › Article › peer-review

Abstract

Preeclampsia, a pregnancy complication characterized by hypertension after 20 gestational weeks, is a major cause of maternal and neonatal morbidity and mortality. Mechanisms leading to preeclampsia are unclear; however, there is evidence of high heritability. We evaluated the association of polygenic scores (PGS) for blood pressure traits and preeclampsia to assess whether there is shared genetic architecture. Non-Hispanic Black and White reproductive age females with pregnancy indications and genotypes were obtained from Vanderbilt University’s BioVU, Electronic Medical Records and Genomics network, and Penn Medicine Biobank. Preeclampsia was defined by ICD codes. Summary statistics for diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) PGS were acquired from Giri et al. Associations between preeclampsia and each PGS were evaluated separately by race and data source before subsequent meta-analysis. Ten-fold cross validation was used for prediction modeling. In 3504 Black and 5009 White included individuals, the rate of preeclampsia was 15.49%. In cross-ancestry meta-analysis, all PGSs were associated with preeclampsia (OR_DBP = 1.10, 95% CI 1.02–1.17, p = 7.68 × 10⁻³; OR_SBP = 1.16, 95% CI 1.09–1.23, p = 2.23 × 10⁻⁶; OR_PP = 1.14, 95% CI 1.07–1.27, p = 9.86 × 10⁻⁵). Addition of PGSs to clinical prediction models did not improve predictive performance. Genetic factors contributing to blood pressure regulation in the general population also predispose to preeclampsia.

Original language	English (US)
Article number	17613
Journal	Scientific reports
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41598-024-68469-6
State	Published - Dec 2024

Funding

Drs. Elizabeth A. Jasper and Jacklyn N. Hellwege are supported by the NIH Building Interdisciplinary Research Career's in Women's Health career development program (K12HD043483 PIs: K.E. Hartmann, A.S. Major, and D.R. Velez Edwards). Dr. Jasper was also supported by a National Human Genome Research Institute award for the Vanderbilt Genomic Medicine Training Program (T32HG008341 PIs: J.F. Peterson, N. Cox, and D.M. Roden). Joseph H. Breeyear was supported by Vanderbilt University Medical Center\u2019s Clinical and Translational Award training program (TL1-TR002244 PI: K.E. Hartmann). Iftikhar J. Kullo is funded by grants HG006379 and HG011710 from the National Human Genome Research Institute and K24HL137010 from the National Heart Lung and Blood Institute. BioVU: The dataset(s) used for the analyses described were obtained from Vanderbilt University Medical Center\u2019s BioVU which is supported by numerous sources: institutional funding, private agencies, and federal grants. These include the NIH funded Shared Instrumentation Grant S10RR025141; and CTSA grants UL1TR002243, UL1TR000445, and UL1RR024975. Genomic data are also supported by investigator-led projects that include U01HG004798, R01NS032830, RC2GM092618, P50GM115305, U01HG006378, U19HL065962, R01HD074711; and additional funding sources listed at https://victr.vumc.org/biovu-funding/. eMERGE Network (Phase III): This phase of the eMERGE Network was initiated and funded by the NHGRI through the following grants: U01HG008657 (Group Health Cooperative/University of Washington); U01HG008685 (Brigham and Women\u2019s Hospital); U01HG008672 (Vanderbilt University Medical Center); U01HG008666 (Cincinnati Children\u2019s Hospital Medical Center); U01HG006379 (Mayo Clinic); U01HG008679 (Geisinger Clinic); U01HG008680 (Columbia University Health Sciences); U01HG008684 (Children\u2019s Hospital of Philadelphia); U01HG008673 (Northwestern University); U01HG008701 (Vanderbilt University Medical Center serving as the Coordinating Center); U01HG008676 (Partners Healthcare/Broad Institute); U01HG008664 (Baylor College of Medicine); and U54MD007593 (Meharry Medical College). eMERGE Network (Phase IV): This phase of the eMERGE Network was initiated and funded by the NHGRI through the following grants: U01HG011172 (Cincinnati Children\u2019s Hospital Medical Center); U01HG011175 (Children\u2019s Hospital of Philadelphia); U01HG008680 (Columbia University); U01HG011176 (Icahn School of Medicine at Mount Sinai); U01HG008685 (Mass General Brigham); U01HG006379 (Mayo Clinic); U01HG011169 (Northwestern University); U01HG011167 (University of Alabama at Birmingham); U01HG008657 (University of Washington Medical Center); U01HG011181 (Vanderbilt University Medical Center); U01HG011166 (Vanderbilt University Medical Center serving as the Coordinating Center).

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10.1038/s41598-024-68469-6

Cite this

Jasper, E. A., Hellwege, J. N., Breeyear, J. H., Xiao, B., Jarvik, G. P., Stanaway, I. B., Leppig, K. A., Chittoor, G., Hayes, M. G., Dikilitas, O., Kullo, I. J., Holm, I. A., Verma, S. S., Edwards, T. L., & Velez Edwards, D. R. (2024). Genetic predictors of blood pressure traits are associated with preeclampsia. Scientific reports, 14(1), Article 17613. https://doi.org/10.1038/s41598-024-68469-6

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title = "Genetic predictors of blood pressure traits are associated with preeclampsia",

abstract = "Preeclampsia, a pregnancy complication characterized by hypertension after 20 gestational weeks, is a major cause of maternal and neonatal morbidity and mortality. Mechanisms leading to preeclampsia are unclear; however, there is evidence of high heritability. We evaluated the association of polygenic scores (PGS) for blood pressure traits and preeclampsia to assess whether there is shared genetic architecture. Non-Hispanic Black and White reproductive age females with pregnancy indications and genotypes were obtained from Vanderbilt University{\textquoteright}s BioVU, Electronic Medical Records and Genomics network, and Penn Medicine Biobank. Preeclampsia was defined by ICD codes. Summary statistics for diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) PGS were acquired from Giri et al. Associations between preeclampsia and each PGS were evaluated separately by race and data source before subsequent meta-analysis. Ten-fold cross validation was used for prediction modeling. In 3504 Black and 5009 White included individuals, the rate of preeclampsia was 15.49%. In cross-ancestry meta-analysis, all PGSs were associated with preeclampsia (ORDBP = 1.10, 95% CI 1.02–1.17, p = 7.68 × 10−3; ORSBP = 1.16, 95% CI 1.09–1.23, p = 2.23 × 10−6; ORPP = 1.14, 95% CI 1.07–1.27, p = 9.86 × 10−5). Addition of PGSs to clinical prediction models did not improve predictive performance. Genetic factors contributing to blood pressure regulation in the general population also predispose to preeclampsia.",

author = "Jasper, {Elizabeth A.} and Hellwege, {Jacklyn N.} and Breeyear, {Joseph H.} and Brenda Xiao and Jarvik, {Gail P.} and Stanaway, {Ian B.} and Leppig, {Kathleen A.} and Geetha Chittoor and Hayes, {M. Geoffrey} and Ozan Dikilitas and Kullo, {Iftikhar J.} and Holm, {Ingrid A.} and Verma, {Shefali Setia} and Edwards, {Todd L.} and {Velez Edwards}, {Digna R.}",

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doi = "10.1038/s41598-024-68469-6",

language = "English (US)",

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T1 - Genetic predictors of blood pressure traits are associated with preeclampsia

AU - Jasper, Elizabeth A.

AU - Hellwege, Jacklyn N.

AU - Breeyear, Joseph H.

AU - Xiao, Brenda

AU - Jarvik, Gail P.

AU - Stanaway, Ian B.

AU - Leppig, Kathleen A.

AU - Chittoor, Geetha

AU - Hayes, M. Geoffrey

AU - Dikilitas, Ozan

AU - Kullo, Iftikhar J.

AU - Holm, Ingrid A.

AU - Verma, Shefali Setia

AU - Edwards, Todd L.

AU - Velez Edwards, Digna R.

PY - 2024/12

Y1 - 2024/12

N2 - Preeclampsia, a pregnancy complication characterized by hypertension after 20 gestational weeks, is a major cause of maternal and neonatal morbidity and mortality. Mechanisms leading to preeclampsia are unclear; however, there is evidence of high heritability. We evaluated the association of polygenic scores (PGS) for blood pressure traits and preeclampsia to assess whether there is shared genetic architecture. Non-Hispanic Black and White reproductive age females with pregnancy indications and genotypes were obtained from Vanderbilt University’s BioVU, Electronic Medical Records and Genomics network, and Penn Medicine Biobank. Preeclampsia was defined by ICD codes. Summary statistics for diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) PGS were acquired from Giri et al. Associations between preeclampsia and each PGS were evaluated separately by race and data source before subsequent meta-analysis. Ten-fold cross validation was used for prediction modeling. In 3504 Black and 5009 White included individuals, the rate of preeclampsia was 15.49%. In cross-ancestry meta-analysis, all PGSs were associated with preeclampsia (ORDBP = 1.10, 95% CI 1.02–1.17, p = 7.68 × 10−3; ORSBP = 1.16, 95% CI 1.09–1.23, p = 2.23 × 10−6; ORPP = 1.14, 95% CI 1.07–1.27, p = 9.86 × 10−5). Addition of PGSs to clinical prediction models did not improve predictive performance. Genetic factors contributing to blood pressure regulation in the general population also predispose to preeclampsia.

AB - Preeclampsia, a pregnancy complication characterized by hypertension after 20 gestational weeks, is a major cause of maternal and neonatal morbidity and mortality. Mechanisms leading to preeclampsia are unclear; however, there is evidence of high heritability. We evaluated the association of polygenic scores (PGS) for blood pressure traits and preeclampsia to assess whether there is shared genetic architecture. Non-Hispanic Black and White reproductive age females with pregnancy indications and genotypes were obtained from Vanderbilt University’s BioVU, Electronic Medical Records and Genomics network, and Penn Medicine Biobank. Preeclampsia was defined by ICD codes. Summary statistics for diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) PGS were acquired from Giri et al. Associations between preeclampsia and each PGS were evaluated separately by race and data source before subsequent meta-analysis. Ten-fold cross validation was used for prediction modeling. In 3504 Black and 5009 White included individuals, the rate of preeclampsia was 15.49%. In cross-ancestry meta-analysis, all PGSs were associated with preeclampsia (ORDBP = 1.10, 95% CI 1.02–1.17, p = 7.68 × 10−3; ORSBP = 1.16, 95% CI 1.09–1.23, p = 2.23 × 10−6; ORPP = 1.14, 95% CI 1.07–1.27, p = 9.86 × 10−5). Addition of PGSs to clinical prediction models did not improve predictive performance. Genetic factors contributing to blood pressure regulation in the general population also predispose to preeclampsia.

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Genetic predictors of blood pressure traits are associated with preeclampsia

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UN SDGs

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