Associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy.
Journal
Journal of hypertension
ISSN: 1473-5598
Titre abrégé: J Hypertens
Pays: Netherlands
ID NLM: 8306882
Informations de publication
Date de publication:
01 03 2023
01 03 2023
Historique:
entrez:
22
3
2023
pubmed:
23
3
2023
medline:
25
3
2023
Statut:
ppublish
Résumé
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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 36947680
doi: 10.1097/HJH.0000000000003336
pii: 00004872-202303000-00002
pmc: PMC9894151
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
380-387Subventions
Organisme : NIA NIH HHS
ID : U54 AG065141
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL136853
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL153382
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.
Références
BJOG. 2018 Dec;125(13):1642-1654
pubmed: 29978553
Nat Genet. 2019 Jan;51(1):51-62
pubmed: 30578418
Nat Genet. 2017 Mar;49(3):403-415
pubmed: 28135244
PLoS One. 2015 Jun 25;10(6):e0131603
pubmed: 26110887
BMJ. 2016 Apr 19;353:i1753
pubmed: 27094586
JAMA. 2021 Sep 28;326(12):1192-1206
pubmed: 34581730
Eur J Obstet Gynecol Reprod Biol. 2013 Sep;170(1):1-7
pubmed: 23746796
JAMA Cardiol. 2019 Jul 1;4(7):628-635
pubmed: 31188397
Nat Commun. 2019 Apr 16;10(1):1776
pubmed: 30992449
Hypertension. 2021 Sep;78(4):927-935
pubmed: 34397272
Scand J Public Health. 2012 Aug;40(6):505-15
pubmed: 22899561
Hypertension. 2022 Feb;79(2):e21-e41
pubmed: 34905954
N Engl J Med. 2022 May 12;386(19):1781-1792
pubmed: 35363951
Am J Obstet Gynecol. 2022 Feb;226(2S):S954-S962
pubmed: 33771361
Hypertension. 2013 Feb;61(2):319-26
pubmed: 23232644
Cardiology. 2020;145(10):633-647
pubmed: 32841945
Nat Med. 2020 Apr;26(4):549-557
pubmed: 32273609
J Clin Hypertens (Greenwich). 2016 Mar;18(3):181-6
pubmed: 26435379
Am J Hypertens. 2016 Jan;29(1):17-24
pubmed: 26002928
N Engl J Med. 2001 Mar 22;344(12):867-72
pubmed: 11259719
Hypertension. 2018 Aug;72(2):408-416
pubmed: 29967039
Semin Perinatol. 2009 Jun;33(3):130-7
pubmed: 19464502
Nat Commun. 2020 Nov 25;11(1):5976
pubmed: 33239696
Nat Genet. 2017 Aug;49(8):1255-1260
pubmed: 28628106
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
Lancet. 2021 Jul 24;398(10297):341-354
pubmed: 34051884
Am J Med Genet A. 2004 Nov 1;130A(4):365-71
pubmed: 15384082
Eur J Epidemiol. 2013 Jan;28(1):1-19
pubmed: 23397514
Obstet Gynecol. 2013 Nov;122(5):1122-1131
pubmed: 24150027
Ann Hum Genet. 2013 Jul;77(4):277-87
pubmed: 23551011
Hypertension. 2011 Dec;58(6):1079-85
pubmed: 22025373
J Pregnancy. 2022 Feb 14;2022:3851225
pubmed: 35198246
Hypertension. 2013 May;61(5):987-94
pubmed: 23509078
PLoS Med. 2015 Mar 31;12(3):e1001779
pubmed: 25826379
Am J Hypertens. 2015 Jul;28(7):915-23
pubmed: 25523295
Nature. 2011 Sep 11;478(7367):103-9
pubmed: 21909115
PLoS One. 2012;7(3):e33666
pubmed: 22432041
Hypertension. 2022 Sep;79(9):2008-2015
pubmed: 35862124
BMC Pregnancy Childbirth. 2012 Jun 29;12:61
pubmed: 22748001
Circulation. 2012 Jul 24;126(4):402-9
pubmed: 22718800
Hypertension. 2019 Mar;73(3):522-531
pubmed: 30712425
BMJ. 2007 Nov 10;335(7627):974
pubmed: 17975258