TY - JOUR
T1 - Polygenic prediction of preeclampsia and gestational hypertension
AU - Honigberg, Michael C.
AU - Truong, Buu
AU - Khan, Raiyan R.
AU - Xiao, Brenda
AU - Bhatta, Laxmi
AU - Vy, Ha My T.
AU - Guerrero, Rafael F.
AU - Schuermans, Art
AU - Selvaraj, Margaret Sunitha
AU - Patel, Aniruddh P.
AU - Koyama, Satoshi
AU - Cho, So Mi Jemma
AU - Vellarikkal, Shamsudheen Karuthedath
AU - Trinder, Mark
AU - Urbut, Sarah M.
AU - Gray, Kathryn J.
AU - Brumpton, Ben M.
AU - Patil, Snehal
AU - Zöllner, Sebastian
AU - Antopia, Mariah C.
AU - Saxena, Richa
AU - Nadkarni, Girish N.
AU - Do, Ron
AU - Yan, Qi
AU - Pe’er, Itsik
AU - Verma, Shefali Setia
AU - Gupta, Rajat M.
AU - Haas, David M.
AU - Martin, Hilary C.
AU - van Heel, David A.
AU - Laisk, Triin
AU - Natarajan, Pradeep
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023/6
Y1 - 2023/6
N2 - Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse maternal and child outcomes. Current tools for prediction, prevention and treatment are limited. Here we tested the association of maternal DNA sequence variants with preeclampsia in 20,064 cases and 703,117 control individuals and with gestational hypertension in 11,027 cases and 412,788 control individuals across discovery and follow-up cohorts using multi-ancestry meta-analysis. Altogether, we identified 18 independent loci associated with preeclampsia/eclampsia and/or gestational hypertension, 12 of which are new (for example, MTHFR–CLCN6, WNT3A, NPR3, PGR and RGL3), including two loci (PLCE1 and FURIN) identified in the multitrait analysis. Identified loci highlight the role of natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development and immune dysregulation. We derived genome-wide polygenic risk scores that predicted preeclampsia/eclampsia and gestational hypertension in external cohorts, independent of clinical risk factors, and reclassified eligibility for low-dose aspirin to prevent preeclampsia. Collectively, these findings provide mechanistic insights into the hypertensive disorders of pregnancy and have the potential to advance pregnancy risk stratification.
AB - Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse maternal and child outcomes. Current tools for prediction, prevention and treatment are limited. Here we tested the association of maternal DNA sequence variants with preeclampsia in 20,064 cases and 703,117 control individuals and with gestational hypertension in 11,027 cases and 412,788 control individuals across discovery and follow-up cohorts using multi-ancestry meta-analysis. Altogether, we identified 18 independent loci associated with preeclampsia/eclampsia and/or gestational hypertension, 12 of which are new (for example, MTHFR–CLCN6, WNT3A, NPR3, PGR and RGL3), including two loci (PLCE1 and FURIN) identified in the multitrait analysis. Identified loci highlight the role of natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development and immune dysregulation. We derived genome-wide polygenic risk scores that predicted preeclampsia/eclampsia and gestational hypertension in external cohorts, independent of clinical risk factors, and reclassified eligibility for low-dose aspirin to prevent preeclampsia. Collectively, these findings provide mechanistic insights into the hypertensive disorders of pregnancy and have the potential to advance pregnancy risk stratification.
UR - http://www.scopus.com/inward/record.url?scp=85160428733&partnerID=8YFLogxK
U2 - 10.1038/s41591-023-02374-9
DO - 10.1038/s41591-023-02374-9
M3 - Article
AN - SCOPUS:85160428733
SN - 1078-8956
VL - 29
SP - 1540
EP - 1549
JO - Nature Medicine
JF - Nature Medicine
IS - 6
ER -