ArticleNature cardiovascular research2024
Genetically proxied HTRA1 protease activity and circulating levels independently predict risk of ischemic stroke and coronary artery disease.
Article in Nature cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Integrative multi-omics analysis identifies endocrine-disrupting chemical-related molecular mechanisms in migraine.The journal of headache and pain · 2026Article
- UK Biobank at 20 - a growing, global resource for dementia research.Nature reviews. Neurology · 2026Review
- Unravelling the genetic architecture of cerebral small vessel disease in the context of stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Explainable retinal deep learning for cardiovascular risk stratification: a multiple modality analysis framework with vascular-centric interpretability and robustness.BMC medical informatics and decision making · 2026Article
- Genetically supported mediators linking peripheral metabolism to cerebral ischemia: a multi-omics characterization of HMGCR, TLR4, and MMP9 in angina pectoris and stroke.Briefings in functional genomics · 2026Article
- Human papillomavirus E7 inhibits immune responses in keratinocytes by activating HTRA1‑mediated mitophagy.International journal of molecular medicine · 2026Article
- Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.Nature aging · 2025Article
- Rare Variants in HTRA1, SGTB, and RBM12 Confer Risk of Atherosclerotic Cardiovascular Disease Independent of Traditional Cardiovascular Risk Factors.Circulation. Genomic and precision medicine · 2025Article
- Monogenic causes of cerebral small vessel disease- models for vascular cognitive impairment and dementia?Current opinion in psychiatry · 2025Review
- Integrative multi-omics analysis of IFNγ-induced macrophages and atherosclerotic plaques reveals macrophage-dependent STAT1-driven transcription in atherosclerosis.Frontiers in immunology · 2025Article
- Identification of biomarkers and immune microenvironment associated with heart failure through bioinformatics and machine learning.Frontiers in molecular biosciences · 2025Article
- ExploringBiomedicines · 2024Review
- Pathophysiology of cerebral small vessel disease: a journey through recent discoveries.The Journal of clinical investigation · 2024Review
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic variants in HTRA1 are associated with stroke risk. However, the mechanisms mediating this remain largely unknown, as does the full spectrum of phenotypes associated with genetic variation in HTRA1. Here we show that rare HTRA1 variants are linked to ischemic stroke in the UK Biobank and BioBank Japan. Integrating data from biochemical experiments, we next show that variants causing loss of protease function associated with ischemic stroke, coronary artery disease and skeletal traits in the UK Biobank and MyCode cohorts. Moreover, a common variant modulating circulating HTRA1 mRNA and protein levels enhances the risk of ischemic stroke and coronary artery disease while lowering the risk of migraine and macular dystrophy in genome-wide association study, UK Biobank, MyCode and BioBank Japan data. We found no interaction between proxied HTRA1 activity and levels. Our findings demonstrate the role of HTRA1 for cardiovascular diseases and identify two mechanisms as potential targets for therapeutic interventions.
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