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Associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy

BACKGROUND: Preexisting hypertension increases risk for preeclampsia. We examined whether a generic blood pressure polygenic risk score (BP-PRS), compared with a preeclampsia-specific polygenic risk score (PE-PRS), could better predict hypertensive disorders of pregnancy. METHODS: Our study sample i...

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Autores principales: Nurkkala, Jouko, Kauko, Anni, FinnGen, Laivuori, Hannele, Saarela, Tanja, Tyrmi, Jaakko S., Vaura, Felix, Cheng, Susan, Bello, Natalie A., Aittokallio, Jenni, Niiranen, Teemu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9894151/
https://www.ncbi.nlm.nih.gov/pubmed/36947680
http://dx.doi.org/10.1097/HJH.0000000000003336
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author Nurkkala, Jouko
Kauko, Anni
FinnGen,
Laivuori, Hannele
Saarela, Tanja
Tyrmi, Jaakko S.
Vaura, Felix
Cheng, Susan
Bello, Natalie A.
Aittokallio, Jenni
Niiranen, Teemu
author_facet Nurkkala, Jouko
Kauko, Anni
FinnGen,
Laivuori, Hannele
Saarela, Tanja
Tyrmi, Jaakko S.
Vaura, Felix
Cheng, Susan
Bello, Natalie A.
Aittokallio, Jenni
Niiranen, Teemu
author_sort Nurkkala, Jouko
collection PubMed
description BACKGROUND: Preexisting hypertension increases risk for preeclampsia. We examined whether a generic blood pressure polygenic risk score (BP-PRS), compared with a preeclampsia-specific polygenic risk score (PE-PRS), could better predict hypertensive disorders of pregnancy. METHODS: Our study sample included 141 298 genotyped FinnGen study participants with at least one childbirth and followed from 1969 to 2021. We calculated PRSs for SBP and preeclampsia using summary statistics for greater than 1.1 million single nucleotide polymorphisms. RESULTS: We observed 8488 cases of gestational hypertension (GHT) and 6643 cases of preeclampsia. BP-PRS was associated with GHT [multivariable-adjusted hazard ratio for 1SD increase in PRS (hazard ratio 1.38; 95% CI 1.35–1.41)] and preeclampsia (1.26, 1.23–1.29), respectively. The PE-PRS was also associated with GHT (1.16; 1.14–1.19) and preeclampsia (1.21, 1.18–1.24), but with statistically more modest magnitudes of effect (P = 0.01). The model c-statistic for preeclampsia improved when PE-PRS was added to clinical risk factors (P = 4.6 × 10(–15)). Additional increment in the c-statistic was observed when BP-PRS was added to a model already including both clinical risk factors and PE-PRS (P = 1.1 × 10(–14)). CONCLUSION: BP-PRS is strongly associated with hypertensive disorders of pregnancy. Our current observations suggest that the BP-PRS could capture the genetic architecture of preeclampsia better than the current PE-PRSs. These findings also emphasize the common pathways in the development of all BP disorders. The clinical utility of a BP-PRS for preeclampsia prediction warrants further investigation.
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spelling pubmed-98941512023-02-07 Associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy Nurkkala, Jouko Kauko, Anni FinnGen, Laivuori, Hannele Saarela, Tanja Tyrmi, Jaakko S. Vaura, Felix Cheng, Susan Bello, Natalie A. Aittokallio, Jenni Niiranen, Teemu J Hypertens Original Articles BACKGROUND: Preexisting hypertension increases risk for preeclampsia. We examined whether a generic blood pressure polygenic risk score (BP-PRS), compared with a preeclampsia-specific polygenic risk score (PE-PRS), could better predict hypertensive disorders of pregnancy. METHODS: Our study sample included 141 298 genotyped FinnGen study participants with at least one childbirth and followed from 1969 to 2021. We calculated PRSs for SBP and preeclampsia using summary statistics for greater than 1.1 million single nucleotide polymorphisms. RESULTS: We observed 8488 cases of gestational hypertension (GHT) and 6643 cases of preeclampsia. BP-PRS was associated with GHT [multivariable-adjusted hazard ratio for 1SD increase in PRS (hazard ratio 1.38; 95% CI 1.35–1.41)] and preeclampsia (1.26, 1.23–1.29), respectively. The PE-PRS was also associated with GHT (1.16; 1.14–1.19) and preeclampsia (1.21, 1.18–1.24), but with statistically more modest magnitudes of effect (P = 0.01). The model c-statistic for preeclampsia improved when PE-PRS was added to clinical risk factors (P = 4.6 × 10(–15)). Additional increment in the c-statistic was observed when BP-PRS was added to a model already including both clinical risk factors and PE-PRS (P = 1.1 × 10(–14)). CONCLUSION: BP-PRS is strongly associated with hypertensive disorders of pregnancy. Our current observations suggest that the BP-PRS could capture the genetic architecture of preeclampsia better than the current PE-PRSs. These findings also emphasize the common pathways in the development of all BP disorders. The clinical utility of a BP-PRS for preeclampsia prediction warrants further investigation. Lippincott Williams & Wilkins 2023-03 2022-12-16 /pmc/articles/PMC9894151/ /pubmed/36947680 http://dx.doi.org/10.1097/HJH.0000000000003336 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Original Articles
Nurkkala, Jouko
Kauko, Anni
FinnGen,
Laivuori, Hannele
Saarela, Tanja
Tyrmi, Jaakko S.
Vaura, Felix
Cheng, Susan
Bello, Natalie A.
Aittokallio, Jenni
Niiranen, Teemu
Associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy
title Associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy
title_full Associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy
title_fullStr Associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy
title_full_unstemmed Associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy
title_short Associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy
title_sort associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9894151/
https://www.ncbi.nlm.nih.gov/pubmed/36947680
http://dx.doi.org/10.1097/HJH.0000000000003336
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