Expressive

rs116015634 - KCNQ4

Magnitude 2.2 · 7 studies on file

Reported associations

  • Genome-wide association and Mendelian randomization analysis provide insights into the shared genetic architecture between high-dimensional electrocardiographic features and ischemic heart disease. - Human genetics (2024) · Wang X, Qi M, Zhang H, Yang Y, Zhao H · PubMed 38180560

    Observational studies have revealed that ischemic heart disease (IHD) has a unique manifestation on electrocardiographic (ECG). However, the genetic relationships between IHD and ECG remain unclear. We took 12-lead ECG as phenotypes to conduct genome-wide association studies (GWAS) for 41,960 samples from UK-Biobank (UKB). By leveraging large-scale GWAS summary of ECG and IHD (downloaded from FinnGen database), we performed LD score regression (LDSC), Mendelian randomization (MR), and polygenic risk score (PRS) regression to explore genetic relationships between IHD and ECG. Finally, we constructed an XGBoost model to predict IHD by integrating PRS and ECG. The GWAS identified 114 independent SNPs significantly (P value < 5 × 10-8/800, where 800 denotes the number of ECG features)

  • Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disorders - Unknown journal (n.d.) · Unknown authors · PubMed 34274964

    ABSTRACT: Abstract The resting QT interval, an electrocardiographic (ECG) measure of ventricular myocardial repolarization, is a heritable risk marker of cardiovascular mortality, but the mechanisms remain incompletely understood. Previously reported candidate genes have provided insights into the regulatory mechanisms of the QT interval. However, there are still important knowledge gaps. We aimed to gain new insights by (i) providing new candidate genes, (ii) identifying pleiotropic associations with other cardiovascular traits, and (iii) scanning for sexually dimorphic genetic effects. We conducted a genome-wide association analysis for resting QT interval with ~9.8 million variants in 52 107 individuals of European ancestry without known cardiovascular disease from the UK Biobank. We

  • Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways - Unknown journal (n.d.) · Unknown authors · PubMed 36050321

    ABSTRACT: The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for ce

  • 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

  • Genetic Basis and Prognostic Value of Exercise QT Dynamics - Unknown journal (n.d.) · Unknown authors · PubMed 32527199

    ABSTRACT: Supplemental Digital Content is available in the text. Background: Abnormal QT interval responses to heart rate (QT dynamics) is an independent risk predictor for cardiovascular disease in patients, but its genetic basis and prognostic value in a population-based cohort have not been investigated. Methods: QT dynamics during exercise and recovery were derived in 56 643 individuals from UK Biobank without a history of cardiovascular events. Genome-wide association studies were conducted to identify genetic variants and bioinformatics analyses were performed to prioritize candidate genes. The prognostic value of QT dynamics was evaluated for cardiovascular events (death or hospitalization) and all-cause mortality. Results: Heritability of QT dynamics during exercise and recovery

  • Cross-modal autoencoder framework learns holistic representations of cardiovascular state - Unknown journal (n.d.) · Unknown authors · PubMed 37105979

    ABSTRACT: A fundamental challenge in diagnostics is integrating multiple modalities to develop a joint characterization of physiological state. Using the heart as a model system, we develop a cross-modal autoencoder framework for integrating distinct data modalities and constructing a holistic representation of cardiovascular state. In particular, we use our framework to construct such cross-modal representations from cardiac magnetic resonance images (MRIs), containing structural information, and electrocardiograms (ECGs), containing myoelectric information. We leverage the learned cross-modal representation to (1) improve phenotype prediction from a single, accessible phenotype such as ECGs; (2) enable imputation of hard-to-acquire cardiac MRIs from easy-to-acquire ECGs; and (3) develop

  • Monogenic and Polygenic Contributions to QTc Prolongation in the Population - Unknown journal (n.d.) · Unknown authors · PubMed 35389749

    ABSTRACT: Background: Rare sequence variation in genes underlying cardiac repolarization and common polygenic variation influence QT interval duration. However, current clinical genetic testing of individuals with unexplained QT prolongation is restricted to examination of monogenic rare variants. The recent emergence of large-scale biorepositories with sequence data enables examination of the joint contribution of rare and common variation to the QT interval in the population. Methods: We performed a genome wide association study (GWAS) of the QTc in 84,630 United Kingdom Biobank (UKB) participants and created a polygenic risk score (PRS). Among 26,976 participants with whole genome sequencing and electrocardiogram data in the Trans-Omics for Precision Medicine (TOPMed) program, we identi

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