ArticleInternational journal of molecular sciences2022
ICA1L Is Associated with Small Vessel Disease: A Proteome-Wide Association Study in Small Vessel Stroke and Intracerebral Haemorrhage.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Migraine, chronic kidney disease and kidney function: observational and genetic analyses.Human genetics · 2023Pooled it
- A Genome-wide Association Study of Alzheimer's Disease and Dementia in a Large Multi-ancestry Military Cohort Identifies Many New Dementia-Associated Loci.medRxiv : the preprint server for health sciences · 2026Article
- Evaluating the causal effects of circulating plasma proteins on the risk of malignant neoplasms of bone and articular cartilage.The Journal of international medical research · 2026Article
- Association between Alzheimer's disease-related genes and neurodegenerative blood-based biomarkers in Indian adults.Frontiers in aging neuroscience · 2026Article
- Editorial for Special Issue "Cerebrovascular Diseases-From Pathogenesis to Treatment: Opportunities and Challenges".Current issues in molecular biology · 2025Article
- Late Intracerebral Hemorrhage After Successful Endovascular Closure of a Carotid-Cavernous Fistula: A Case Report and Updated Review.Reports (MDPI) · 2025Article
- Characterizing Genetic-Predisposed Proteins Involving Insomnia by Integrating Genome-Wide Association Study Summary Statistics.Molecular neurobiology · 2025Article
- Multi-Ancestry Transcriptome-Wide Association Studies of Cognitive Function, White Matter Hyperintensity, and Alzheimer's Disease.International journal of molecular sciences · 2025Article
- Exploring potential drug targets for SLE through Mendelian randomization and network pharmacology.PloS one · 2025Article
- Identification of Genetic Loci Associated With Intracerebral Hemorrhage Using a Multitrait Analysis Approach.Neurology · 2024Article
- NeuroimaGene: an R package for assessing the neurological correlates of genetically regulated gene expression.BMC bioinformatics · 2024Article
- Molecular Mechanisms and Pathophysiology of Acute Stroke: Recent Advances and Controversies.Current issues in molecular biology · 2024Article
- Gender Predicts Differences in Acute Ischemic Cardioembolic Stroke Profile: Emphasis on Woman-Specific Clinical Data and Early Outcome-The Experience of Sagrat Cor Hospital of Barcelona Stroke Registry.Medicina (Kaunas, Lithuania) · 2024Article
- Identifying causal genes for migraine by integrating the proteome and transcriptome.The journal of headache and pain · 2023Article
- Identifying novel proteins underlying loneliness by integrating GWAS summary data with human brain proteomes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Article
- Brain proteome-wide association study linking-genes in multiple sclerosis pathogenesis.Annals of clinical and translational neurology · 2023Article
- Vertigo in Acute Stroke Is a Predictor of Brain Location but Is Not Related to Early Outcome: The Experience of Sagrat Cor Hospital of Barcelona Stroke Registry.Biomedicines · 2022Article
- Molecular Mechanisms and Pathophysiology of Acute Stroke: Emphasis on Biomarkers in the Different Stroke Subtypes.International journal of molecular sciences · 2022Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Small vessel strokes (SVS) and intracerebral haemorrhages (ICH) are acute outcomes of cerebral small vessel disease (SVD). Genetic studies combining both phenotypes have identified three loci associated with both traits. However, the genetic cis-regulation at the protein level associated with SVD has not been studied before. We performed a proteome-wide association study (PWAS) using FUSION to integrate a genome-wide association study (GWAS) and brain proteomic data to discover the common mechanisms regulating both SVS and ICH. Dorsolateral prefrontal cortex (dPFC) brain proteomes from the ROS/MAP study (N = 376 subjects and 1443 proteins) and the summary statistics for the SVS GWAS from the MEGASTROKE study (N = 237,511) and multi-trait analysis of GWAS (MTAG)-ICH−SVS from Chung et al. (N = 240,269) were selected. We performed PWAS and then a co-localization analysis with COLOC. The significant and nominal results were validated using a replication dPFC proteome (N = 152). The replicated results (q-value < 0.05) were further investigated for the causality relationship using summary data-based Mendelian randomization (SMR). One protein (ICA1L) was significantly associated with SVS (z-score = −4.42 and p-value = 9.6 × 10−6) and non-lobar ICH (z-score = −4.8 and p-value = 1.58 × 10−6) in the discovery PWAS, with a high co-localization posterior probability of 4. In the validation PWAS, ICA1L remained significantly associated with both traits. The SMR results for ICA1L indicated a causal association of protein expression levels in the brain with SVS (p-value = 3.66 × 10−5) and non-lobar ICH (p-value = 1.81 × 10−5). Our results show that the association of ICA1L with SVS and non-lobar ICH is conditioned by the cis-regulation of its protein levels in the brain.
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