Paul J.R. Barton

MAP3K7 Loss of Function Causes Dilated Cardiomyopathy

This paper shows that loss-of-function variants in MAP3K7 cause dilated cardiomyopathy (DCM), both as part of syndromic disease and as apparently isolated DCM.

Loss of the alternative calcineurin variant CnAβ1 enhances brown adipocyte differentiation and drives metabolic overactivation through FoxO1 activation

This study shows that loss of CnAβ1 enhances brown adipocyte differentiation and metabolic activity through FoxO1 activation, leading to improved insulin sensitivity and reduced body weight on a high-fat diet.

Evaluation of polygenic score for hypertrophic cardiomyopathy in the general population and across clinical settings

This study evaluates polygenic scores for hypertrophic cardiomyopathy (HCM) in the general population and clinical settings, showing increased risk with higher scores and potential for clinical application.

Genome-wide association analysis reveals insights into the molecular aetiology underlying dilated cardiomyopathy

This study identifies 80 genetic loci and 61 effector genes associated with dilated cardiomyopathy through GWAS and integrates transcriptomic data to uncover biological pathways and cellular states involved in the disease.

Interleukin 11 therapy causes acute heart failure and its use in patients should be reconsidered

This paper identifies direct cardiomyocyte toxicities of IL11 therapy, showing it causes acute heart failure by activating JAK/STAT3, which questions its continued use in patients.

The penetrance of rare variants in cardiomyopathy-associated genes: a cross-sectional approach to estimate penetrance for secondary findings

This paper estimates the penetrance of rare variants in cardiomyopathy genes using cross-sectional data from genetic testing, finding substantial penetrance for dominant cardiomyopathies and variant-specific differences.

Cardiomyocyte-restricted expression of IL11 causes cardiac fibrosis, inflammation, and dysfunction.

This study shows that IL11 expression in cardiomyocytes causes cardiac fibrosis, inflammation, and dysfunction, contradicting previous reports of its anti-fibrotic effects.

Variant annotation across homologous proteins (Paralogue Annotation) identifies disease-causing missense variants with high precision, and is widely applicable across protein families

This paper introduces Paralogue Annotation, a method using homologous protein variants to predict disease-causing missense variants with high precision.

Outcomes and phenotypic expression of rare variants in hypertrophic cardiomyopathy genes amongst UK Biobank participants

This study examines the clinical impact of rare variants in HCM-associated genes in the UK Biobank, finding that pathogenic variants are linked to increased cardiovascular risk and subclinical phenotypes, while non-pathogenic variants show minimal effect.

Analysis of HCM in an understudied population reveals a new mechanism of pathogenicity

The paper identifies a frameshift variant in MYH7 associated with HCM in an Egyptian cohort, revealing a new pathogenic mechanism involving distal PTC escape from NMD.

Non-coding variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms

The paper identifies non-coding variants upstream of MEF2C causing severe developmental disorder through three distinct loss-of-function mechanisms, showing their diagnostic importance in existing exome datasets.

The genetic architecture of left ventricular non-compaction reveals both substantial overlap with other cardiomyopathies and a distinct aetiology in a subset of cases

This study identifies genetic overlaps and distinct variant classes in LVNC compared to DCM and HCM, revealing both shared and unique genetic mechanisms.

Genomics of Egyptian Healthy Volunteers: The EHVol Study

The paper describes the EHVol study, a genomic database of 391 Egyptian healthy volunteers to improve representation in global genomic databases and aid in variant interpretation for North African populations.

Disease-specific variant pathogenicity prediction significantly improves variant interpretation in inherited cardiac conditions

This paper introduces CardioBoost, a disease-specific variant classifier for inherited cardiac conditions, showing improved accuracy in predicting pathogenicity compared to genome-wide tools.

Translational control of cardiac fibrosis

The paper identifies translational regulators of fibrogenic genes in human cardiac fibroblasts and shows their role in cardiac fibrosis through ribosome profiling and RNA-binding protein analysis.

Quantitative approaches to variant classification increase the yield and precision of genetic testing in Mendelian diseases: The case of hypertrophic cardiomyopathy

The paper quantifies variant pathogenicity in hypertrophic cardiomyopathy using etiological fraction, increasing actionable variant detection by 14-20%.

Response to Shah et al: Using high-resolution variant frequencies empowers clinical genome interpretation and enables investigation of genetic architecture

The paper responds to a critique of their variant filtering method, demonstrating its robustness and highlighting the benefits of using high-resolution variant frequencies for clinical genome interpretation.

CardioClassifier: demonstrating the power of disease- and gene-specific computational decision support for clinical genome interpretation

CardioClassifier is a decision-support tool for inherited cardiac conditions that improves variant interpretation by integrating disease-specific annotations and case data.

Using high-resolution variant frequencies to empower clinical genome interpretation

The paper presents a statistical framework to filter candidate disease-causing variants using high-resolution variant frequencies, reducing the number of variants under consideration and reclassifying some as pathogenic.