Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia

Art Schuermans, Buu Truong, Maddalena Ardissino, Rohan Bhukar, Eric AW Slob, Pradeep Natarajan, Michael C Honigberg

Abstract:

Importance Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease.

Objective To identify proteins in the circulation associated with HDPs.

Design, Setting, and Participants Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease–related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins’ dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP–related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease–related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023.

Exposures Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs).

Main Outcomes and Measures Gestational hypertension and preeclampsia.