rs116904997 - PXN

Magnitude 2.2 · 4 studies on file

Reported associations

• Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect - Unknown journal (n.d.) · Unknown authors · PubMed 33495596

  ABSTRACT: The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young otherwise healthy individuals. We conducted genome-wide association studies (GWAS) and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases), and nine left ventricular (LV) traits in 19,260 UK Biobank participants with structurally normal hearts. We identified 16 loci associated with HCM, 13 with DCM, and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased contractility with HCM risk. A polygenic risk score (PRS) explains a significant portion of phenotypic variability in

• Cross-population GWAS and proteomics improve risk prediction and reveal mechanisms in atrial fibrillation - Unknown journal (n.d.) · Unknown authors · PubMed 40645996

  ABSTRACT: Atrial fibrillation (AF) is a common cardiac arrhythmia with strong genetic components, yet its underlying molecular mechanisms and potential therapeutic targets remain incompletely understood. We conducted a cross-population genome-wide meta-analysis of 252,438 AF cases and identified 525 loci that met genome-wide significance. Two loci of PITX2 and ZFHX3 genes were identified as shared across populations of different ancestries. Comprehensive gene prioritization approaches reinforced the role of muscle development and heart contraction while also uncovering additional pathways, including cellular response to transforming growth factor-beta. Population-specific genetic correlations uncovered common and unique circulatory comorbidities between Europeans and Africans. Mendelian ra

• Genetic analyses across cardiovascular traits: leveraging genetic correlations to empower locus discovery and prediction in common cardiovascular diseases - Unknown journal (n.d.) · Unknown authors · PubMed 41022758

  ABSTRACT: Common genetic variation detected by genome-wide association studies (GWAS) partially explains variability in the spectrum of cardiac phenotypes. In this work, we explore genetic correlations among 58 cardiac-related traits/diseases, detecting novel ones. We subsequently employ multi-trait analysis of GWAS (MTAG), which meta-analyzes genetically correlated traits, to improve genomic loci discovery and prediction in atrial fibrillation (AF), coronary artery disease (CAD), and heart failure (HF). We identify 19 novel loci specific for AF, 131 for CAD, and 141 for HF. Polygenic scores (PGS) in 15,177 Canadian individuals show similar results when PGS are derived from conventional GWAS versus MTAG summary statistics, although MTAG-PGS improve prediction and discrimination of CAD in f

• Large-scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy - Unknown journal (n.d.) · Unknown authors · PubMed 39966646

  ABSTRACT: Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality with both monogenic and polygenic components. Here, we report results from a large genome-wide association study and multitrait analysis including 5,900 HCM cases, 68,359 controls and 36,083 UK Biobank participants with cardiac magnetic resonance imaging. We identified 70 loci (50 novel) associated with HCM and 62 loci (20 novel) associated with relevant left ventricular traits. Among the prioritized genes in the HCM loci, we identify a novel HCM disease gene, SVIL, which encodes the actin-binding protein supervillin, showing that rare truncating SVIL variants confer a roughly tenfold increased risk of HCM. Mendelian randomization analyses support a causal role of increased left ventricular contrac

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