血压性状的遗传预测因子与先兆子痫相关。

Genetic Predictors of Blood Pressure Traits are Associated with Preeclampsia.

作者信息

Jasper Elizabeth A, Hellwege Jacklyn N, Breeyear Joseph H, Xiao Brenda, Jarvik Gail P, Stanaway Ian B, Leppig Kathleen A, Chittoor Geetha, Hayes M Geoffrey, Dikilitas Ozan, Kullo Iftikhar J, Holm Ingrid A, Verma Shefali Setia, Edwards Todd L, Velez Edwards Digna R

出版信息

medRxiv. 2023 Feb 14:2023.02.09.23285734. doi: 10.1101/2023.02.09.23285734.

DOI:10.1101/2023.02.09.23285734

PMID:36824881

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9949198/

Abstract

BACKGROUND

Preeclampsia, a pregnancy complication characterized by hypertension after 20 gestational weeks, is a major cause of maternal and neonatal morbidity and mortality. The mechanisms leading to preeclampsia are unclear; however, there is evidence that preeclampsia is highly heritable. We evaluated the association of polygenic risk scores (PRS) for blood pressure traits and preeclampsia to assess whether there is shared genetic architecture.

METHODS

Participants were obtained from Vanderbilt University's BioVU, the Electronic Medical Records and Genomics network, and the Penn Medicine Biobank. Non-Hispanic Black and White females of reproductive age with indications of pregnancy and genotype information were included. Preeclampsia was defined by ICD codes. Summary statistics for diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) PRS were obtained from Giri et al 2019. Associations between preeclampsia and each PRS were evaluated separately by race and study population before evidence was meta-analyzed. Prediction models were developed and evaluated using 10-fold cross validation.

RESULTS

In the 3,504 Black and 5,009 White individuals included, the rate of preeclampsia was 15.49%. The DBP and SBP PRSs were associated with preeclampsia in Whites but not Blacks. The PP PRS was significantly associated with preeclampsia in Blacks and Whites. In trans-ancestry meta-analysis, all PRSs were associated with preeclampsia (OR =1.10, 95% CI=1.02-1.17, =7.68×10 ; OR =1.16, 95% CI=1.09-1.23, =2.23×10 ; OR =1.14, 95% CI=1.07-1.27, =9.86×10 ). However, addition of PRSs to clinical prediction models did not improve predictive performance.

CONCLUSIONS

Genetic factors contributing to blood pressure regulation in the general population also predispose to preeclampsia.

摘要

背景

子痫前期是一种妊娠并发症，其特征为妊娠20周后出现高血压，是孕产妇和新生儿发病及死亡的主要原因。导致子痫前期的机制尚不清楚；然而，有证据表明子痫前期具有高度遗传性。我们评估了血压性状的多基因风险评分（PRS）与子痫前期的关联，以评估是否存在共同的遗传结构。

方法

参与者来自范德比尔特大学的BioVU、电子病历与基因组学网络以及宾夕法尼亚大学医学生物样本库。纳入有妊娠指征和基因型信息的非西班牙裔黑人和白人育龄女性。子痫前期由国际疾病分类代码定义。舒张期血压（DBP）、收缩期血压（SBP）和脉压（PP）PRS的汇总统计数据来自吉里等人2019年的研究。在进行荟萃分析之前，按种族和研究人群分别评估子痫前期与每个PRS之间的关联。使用10折交叉验证开发并评估预测模型。

结果

在纳入的3504名黑人个体和5009名白人个体中，子痫前期的发生率为15.49%。DBP和SBP PRS与白人的子痫前期相关，但与黑人无关。PP PRS与黑人和白人的子痫前期均显著相关。在跨种族荟萃分析中，所有PRS均与子痫前期相关（比值比=1.10，95%置信区间=1.02-1.17，P=7.68×10⁻³；比值比=1.16，95%置信区间=1.09-1.23，P=2.23×10⁻⁴；比值比=1.14，95%置信区间=1.07-1.27，P=9.86×10⁻³）。然而，将PRS添加到临床预测模型中并未提高预测性能。