SynthesisNeurology2016
Low-frequency and common genetic variation in ischemic stroke: The METASTROKE collaboration.
Synthesis in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 91 papers, 11 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
91 citing papers in PubMed, 11 syntheses or guidelines pooled it.
- Lowering of Circulating Sclerostin May Increase Risk of Atherosclerosis and Its Risk Factors: Evidence From a Genome-Wide Association Meta-Analysis Followed by Mendelian Randomization.Arthritis & rheumatology (Hoboken, N.J.) · 2023Pooled it
- Risk factors and predictors for venous thromboembolism in people with ischemic stroke: A systematic review.Journal of thrombosis and haemostasis : JTH · 2022Pooled it
- Impact of high glucose levels and glucose lowering on risk of ischaemic stroke: a Mendelian randomisation study and meta-analysis.Diabetologia · 2021Pooled it
- Association Between Circulating Proprotein Convertase Subtilisin/Kexin Type 9 and Major Adverse Cardiovascular Events, Stroke, and All-Cause Mortality: Systemic Review and Meta-Analysis.Frontiers in cardiovascular medicine · 2021Pooled it
- Pooled it
- Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.Nature communications · 2019Pooled it
- Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.Nature genetics · 2018Pooled it
- Differential effects of PCSK9 variants on risk of coronary disease and ischaemic stroke.European heart journal · 2018Pooled it
- Pooled it
- Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation.Nature genetics · 2017Pooled it
- The SG13S114 polymorphism of the ALOX5AP gene is associated with ischemic stroke in Europeans: a meta-analysis of 8062 subjects.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2017Pooled it
- The relationship between the prognosis of children with acute arterial stroke and polymorphisms of CDKN2B, HDAC9, NINJ2, NAA25 genes.Journal of thrombosis and thrombolysis · 2019Trial
- Trial
- GlialeLife · 2026Article
- Decoding Stroke Etiology: Multi-Omics Advancements in Genetic Mechanisms and Clinical Implication.Brain and behavior · 2025Review
- Altered DNA methylation of the ABO gene is associated with differential plasma levels of von willebrand factor and E-selectin.Transfusion · 2025Article
- Sarcopenia and Risk of Cognitive Impairment: Cohort Study and Mendelian Randomization Analysis.JMIR aging · 2025Article
- Association between Stroke History and Clinical Events in Atrial Fibrillation Patients after Valve Replacement.Reviews in cardiovascular medicine · 2025Article
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
- Metabolism-Mediated FGF5 Association with Stroke: Based on Mendelian Randomization and Bioinformatics Analysis.Journal of multidisciplinary healthcare · 2025Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
53 authors.
Funding
Abstract
objectiveTo investigate the influence of common and low-frequency genetic variants on the risk of ischemic stroke (all IS) and etiologic stroke subtypes.
methodsWe meta-analyzed 12 individual genome-wide association studies comprising 10,307 cases and 19,326 controls imputed to the 1000 Genomes (1 KG) phase I reference panel. We selected variants showing the highest degree of association (p < 1E-5) in the discovery phase for replication in Caucasian (13,435 cases and 29,269 controls) and South Asian (2,385 cases and 5,193 controls) samples followed by a transethnic meta-analysis. We further investigated the p value distribution for different bins of allele frequencies for all IS and stroke subtypes.
resultsWe showed genome-wide significance for 4 loci: ABO for all IS, HDAC9 for large vessel disease (LVD), and both PITX2 and ZFHX3 for cardioembolic stroke (CE). We further refined the association peaks for ABO and PITX2. Analyzing different allele frequency bins, we showed significant enrichment in low-frequency variants (allele frequency <5%) for both LVD and small vessel disease, and an enrichment of higher frequency variants (allele frequency 10% and 30%) for CE (all p < 1E-5).
conclusionsOur findings suggest that the missing heritability in IS subtypes can in part be attributed to low-frequency and rare variants. Larger sample sizes are needed to identify the variants associated with all IS and stroke subtypes.
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