ArticleBMC medicine2022
Identification of novel proteins for lacunar stroke by integrating genome-wide association data and human brain proteomes.
Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
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Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- Association of methylenetetrahydrofolate reductase C677T polymorphism with lacunar infarction: A systematic review and meta-analysis.Medicine · 2026Pooled it
- Multi-omics and high-spatial-resolution omics: deciphering complexity in neurological disorders.GigaScience · 2025Pooled it
- Genome-wide DNA methylation analysis revealed epigenetic mechanism underlying end-stage renal disease.Nature communications · 2026Article
- CAND1 and CAND2 drive CUL4 substrate receptor exchange with largely comparable biochemical efficiency, unlike their relative effects on CUL1.Structure (London, England : 1993) · 2026Article
- Deciphering cell type-specific causal genetic effects on brain imaging-derived phenotypes and disorders with single-cell Mendelian randomization.PLoS computational biology · 2026Article
- Plasma proteome-genome integration reveals novel protein biomarkers and therapeutic targets linked to breast cancer survival.Archives of medical science : AMS · 2026Article
- Investigating the Mechanisms of Mitochondrial Dysfunction in Ischemic Stroke and Predicting Therapeutics Through Machine Learning and Integrated Bioinformatics.Current medicinal chemistry · 2026Article
- Proteome-wide Mendelian randomization identifies drug targets for atrial fibrillation/flutter.BMC cardiovascular disorders · 2025Article
- Shared genetic architecture between stroke and blood lipids: a large-scale genome-wide cross-trait analysis.Human genomics · 2025Article
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- Identification of novel plasma proteins as potential therapeutic targets for benign prostatic hyperplasia: a proteome-wide association study.Translational andrology and urology · 2025Article
- Characterizing Genetic-Predisposed Proteins Involving Insomnia by Integrating Genome-Wide Association Study Summary Statistics.Molecular neurobiology · 2025Article
- Genetic associations of plasma proteins and breast cancer identify potential therapeutic drug candidates.Communications biology · 2025Article
- Multi-Ancestry Transcriptome-Wide Association Studies of Cognitive Function, White Matter Hyperintensity, and Alzheimer's Disease.International journal of molecular sciences · 2025Article
- Molecular mechanisms of CAND2 in regulating SCF ubiquitin ligases.Nature communications · 2025Article
- Proteome-wide association studies have predicted that the protein abundance of LSM6, GMPPB, ICA1L, and CISD2 is associated with attention-deficit/hyperactivity disorder.European child & adolescent psychiatry · 2025Article
- Proteome-Wide Association Study for Finding Druggable Targets in Progression and Onset of Parkinson's Disease.CNS neuroscience & therapeutics · 2025Article
- Monitoring of single-nucleus chromatin landscape of ischemic stroke in mouse cerebral cortex across time.Scientific data · 2025Article
- Blood biochemical landscape and new insights into clinical decision-making for polycystic ovary syndrome in Chinese women: a prospective cohort study.Frontiers in endocrinology · 2025Article
- NMRAL1 as a Causal Factor in Postherpetic Neuralgia: A Proteome-Wide Mendelian Randomization Study.Journal of pain research · 2025Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrevious genome-wide association studies (GWAS) have identified numerous risk genes for lacunar stroke, but it is challenging to decipher how they confer risk for the disease. We employed an integrative analytical pipeline to efficiently transform genetic associations to identify novel proteins for lacunar stroke.
methodsWe systematically integrated lacunar stroke genome-wide association study (GWAS) (N=7338) with human brain proteomes (N=376) to perform proteome-wide association studies (PWAS), Mendelian randomization (MR), and Bayesian colocalization. We also used an independent human brain proteomic dataset (N=152) to annotate the new genes.
resultsWe found that the protein abundance of seven genes (ICA1L, CAND2, ALDH2, MADD, MRVI1, CSPG4, and PTPN11) in the brain was associated with lacunar stroke. These seven genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and astrocytes. Three genes (ICA1L, CAND2, ALDH2) were causal in lacunar stroke (P < 0.05/proteins identified for PWAS; posterior probability of hypothesis 4 ≥ 75 % for Bayesian colocalization), and they were linked with lacunar stroke in confirmatory PWAS and independent MR. We also found that ICA1L is related to lacunar stroke at the brain transcriptome level.
conclusionsOur present proteomic findings have identified ICA1L, CAND2, and ALDH2 as compelling genes that may give key hints for future functional research and possible therapeutic targets for lacunar stroke.
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