Polygenic prediction of preeclampsia and gestational hypertension.
Michael C HonigbergBuu TruongRaiyan R KhanBrenda XiaoLaxmi BhattaHa My T VyRafael F GuerreroArt SchuermansMargaret Sunitha SelvarajAniruddh P PatelSatoshi KoyamaSo Mi Jemma ChoShamsudheen Karuthedath VellarikkalMark TrinderSarah M UrbutKathryn J Gray GusehBen Michael BrumptonSnehal PatilSebastian ZöllnerMariah C AntopiaRicha SaxenaGirish Nitin NadkarniRon DoQi YanItsik Pe'erShefali Setia VermaRajat M GuptaDavid M HaasHilary C MartinDavid A van HeelTriin LaiskPradeep NatarajanPublished in: Nature medicine (2023)
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.
Keyphrases
- pregnancy outcomes
- blood pressure
- pregnant women
- genome wide
- low dose
- early onset
- weight gain
- risk factors
- systematic review
- birth weight
- dna methylation
- genome wide association study
- stem cells
- mental health
- copy number
- randomized controlled trial
- cell proliferation
- endothelial cells
- metabolic syndrome
- gene expression
- preterm birth
- acute coronary syndrome
- single molecule
- climate change
- insulin resistance
- weight loss
- physical activity
- circulating tumor
- gestational age
- body mass index
- percutaneous coronary intervention
- arterial hypertension