Genetic and methodological considerations in hypertensive disorders of pregnancy and risk of cardiovascular disease

This commentary refers to ‘Preeclampsia, gestational hypertension, and cardiovascular disease risk: a genetic epidemiological study’, by S.T. Nielsen et al., https://doi.org/10.1093/eurheartj/ehaf565 and the discussion piece ‘Overlooked complexities in pregnancy hypertension-CVD genetic studies’, by B.-Y. Yao et al., https://doi.org/10.1093/eurheartj/ehaf931. We appreciate the opportunity to respond to this commentary, as the questions raised by Yao et al. are crucial to fully understand our study and the genetic approach we used in it. Yao et al. provide a clear summary of the conclusion of the study, and we are thankful for their appreciation. They outline three concerns regarding details of the article, which we are pleased to clarify. Firstly, they raised the very relevant point of distinguishing between early- and late-onset preeclampsia. We acknowledge the important clinical and pathological differences between these two types; however, current available genetic data typically combine these subtypes,1,2 thereby constraining the ability to conduct rigorous genetic analyses for causal inferences separately. We strongly advocate for leveraging large-scale genomic studies to identify genetic variants for early- and late-onset preeclampsia to enable future studies elucidating their potential divergent causal impact on risk of cardiovascular disease.