ArticleJAMA cardiology2024
Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.
Article in JAMA cardiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Cardiac remodelling and dysfunction in cancer patients receiving cardiotoxic therapies: proteomic and metabolomic profiling.European heart journal · 2026Article
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- Large-scale proteomics in early pregnancy and timing of onset of hypertensive disorders of pregnancy.medRxiv : the preprint server for health sciences · 2026Article
- Cardiovascular disease in women: traditional and sex-specific risk factors.European heart journal · 2026Review
- Association of borderline hypertension defined by ACC-AHA diagnostic criteria during pregnancy with neurodevelopment in infants.BMC medicine · 2026Article
- Effects of Genetically-Proxied Antihypertensive Drug Targets on Preeclampsia and Birth Weight.medRxiv : the preprint server for health sciences · 2026Article
- Genetic Association of Circulating Proteins and Gene Transcripts With Spontaneous Coronary Artery Dissection.Circulation. Genomic and precision medicine · 2026Article
- NT-proBNP as a Predictive and Prognostic Biomarker for Complications in Hypertensive Pregnancy Disorders.Journal of clinical medicine · 2026Article
- Identifying Novel Biomarkers and Therapeutic Targets for Endometriosis: Integrative Analysis of the Plasma Proteome and Genome.Mediators of inflammation · 2026Article
- Human genetics implicate thromboembolism in the pathogenesis of long COVID in individuals of European ancestry.Nature cardiovascular research · 2025Article
- Machine learning-based prediction of preeclampsia using first-trimester inflammatory markers and red blood cell indices.BMC pregnancy and childbirth · 2025Article
- Effect of magnesium sulfate and personalised dietary guidance on hemodynamics and inflammatory cytokines in pregnancy-induced hypertension.Journal of medical biochemistry · 2025Article
- Proteomic prediction of disease largely reflects environmental risk exposure.medRxiv : the preprint server for health sciences · 2025Article
- Prospective determination of heat shock protein serum levels in Saskatchewan women during pregnancy.AJOG global reports · 2025Article
- Uncovering therapeutic targets for Pre-eclampsia and pregnancy hypertension via multi-tissue data integration.BMC pregnancy and childbirth · 2025Article
- Advances in Our Understanding of Cardiovascular Diseases After Preeclampsia.Circulation research · 2025Review
- Identification of Causal Plasma Proteins in Hepatocellular Carcinoma via Two-Sample Mendelian Randomization and Integrative Transcriptomic‒Proteomic Analysis.Cancer research communications · 2025Article
- Text phrase-mining in identifying and classifying maternal proteins and genes across preeclampsia and similar pathologies.Physiological reports · 2025Article
- Hypertension in Pregnancy and Postpartum: Current Standards and Opportunities to Improve Care.Circulation · 2025Review
- Associations of Genetically Predicted NPR3 and NPR2 Perturbation and Preeclampsia Risk: A Two-Sample Mendelian Randomization Analysis.International journal of hypertension · 2025Article
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Authors and funding
27 authors at 9 institutions in 5 countries.
Funding
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. Results: Genetic association data for cardiovascular disease-related proteins were obtained from 21 758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393 238 female individuals (8636 cases and 384 602 controls) for gestational hypertension and 606 903 female individuals (16 032 cases and 590 871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins. Conclusions and Relevance: Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.
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