Expressive

rs11784619 - PLEC

Magnitude 2.2 · 5 studies on file

Reported associations

  • Combining cross-sectional and longitudinal genomic approaches to identify determinants of cognitive and physical decline - Unknown journal (n.d.) · Unknown authors · PubMed 40374629

    ABSTRACT: Large-scale genomic studies focusing on the genetic contribution to human aging have mostly relied on cross-sectional data. With the release of longitudinally curated aging phenotypes by the UK Biobank (UKBB), it is now possible to study aging over time at genome-wide scale. In this work, we evaluated the suitability of competing models of change in realistic simulation settings, performed genome-wide association scans on simulation-validated measures of age-related deweekcline, and followed up with LD-score regression and Mendelian Randomization (MR) analyses. Focusing on global cognitive and physical function, we observed marked differences between baseline function (θ) and accelerated decline (Δ). Both outcomes showed distinct heritability levels (e.g., 31.38% versus 3.15%

  • The Genetic Makeup of the Electrocardiogram - Unknown journal (n.d.) · Unknown authors · PubMed 32916098

    ABSTRACT: SUMMARY The electrocardiogram (ECG) is one of the most useful non-invasive diagnostic tests for a wide array of cardiac disorders. Traditional approaches to analyzing ECGs focus on individual segments. Here, we performed comprehensive deep phenotyping of 77,190 ECGs in the UK Biobank across the complete cycle of cardiac conduction, resulting in 500 spatial-temporal datapoints, across 10 million genetic variants. In addition to characterizing polygenic risk scores for the traditional ECG segments, we identified over 300 genetic loci that are statistically associated with the high-dimensional representation of the ECG. We established the genetic ECG signature for dilated cardiomyopathy, associated the BAG3, HSPB7/CLCNKA, PRKCA, TMEM43, and OBSCN loci with disease risk and confirmed

  • 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

  • Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity - Unknown journal (n.d.) · Unknown authors · PubMed 37126556

    ABSTRACT: Dysfunction of either the right or left ventricle can lead to heart failure (HF) and subsequent morbidity and mortality. We performed a genome-wide association study (GWAS) of 16 cardiac magnetic resonance (CMR) imaging measurements of biventricular function and structure. Cis-Mendelian randomization (MR) was used to identify plasma proteins associating with CMR traits as well as with any of the following cardiac outcomes: HF, non-ischemic cardiomyopathy, dilated cardiomyopathy (DCM), atrial fibrillation, or coronary heart disease. In total, 33 plasma proteins were prioritized, including repurposing candidates for DCM and/or HF: IL18R (providing indirect evidence for IL18), I17RA, GPC5, LAMC2, PA2GA, CD33, and SLAF7. In addition, 13 of the 25 druggable proteins (52%; 95% confiden

  • 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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