Seung Mi Lee
Genome-wide polygenic risk scores for hypertensive disease during pregnancy identify women at risk for long-term cardiovascular disease
We developed genetic risk score for hypertensive disease during pregnancy, and showed that the developed genetic score was also predictive of long-term cardiovascular outcomes
Background&Aims: Previous studies suggest that hypertensive disease during pregnancy (HDP) increase the risk of long-term cardiovascular disease later in life, and clinical guidelines recommend including HDP as an important female-specific factor in risk assessment. In this study, we developed polygenic risk scores for HDP (HDP-PRS) and evaluated its impact on long-term cardiovascular outcomes.
Methods: From the UK biobank, we included unrelated Caucasian women with at least one live birth and available genetic data. HDP-PRS was calculated by LDpred using the summary statistics from FinnGen, another large-scale biobank. Subjects were divided according to the genetic risk categorized by HDP-PRS and were evaluated for incident cardiovascular disease.
Results: Among 165,333 women, 2,441 reported a history of HDP and a total of 9,888 women developed new-onset cardiovascular disease after enrollment. Women with high genetic risk for HDP (HPP-PRS>75p) reported higher frequency of a HDP and had a higher prevalence of hypertension at enrollment. After enrollment, women with high genetic risk for HDP had increased risk for subsequent cardiovascular diseases, including coronary artery disease (p<0.05), myocardial infarction (p<0.005), heart failure (p<0.005), and aortic stenosis (p<0.05), compared to those with lower genetic risk (HDP-PRS<75p). This relationship remained significant even after adjustment for history of HDP and other covariates, including age, BMI, smoking, and prevalent metabolic disease.
Conclusions: This study provides evidence on the informative value of HDP-PRS in the prediction of long-term cardiovascular outcomes later in life. The application of PRS information for risk assessment and medical interventions needs to be evaluated in further studies.
Keywordshypertensive disease during pregnancy, preeclampsia, long-term outcomes, cardiovascular outcome, polygenic risk score
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