Declan P. O’Regan

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.

Genetic architecture of cardiac structure and function

This study identifies 42 genetic loci associated with cardiac structure and contractility using a spatially-resolved genome-wide association study in 47,549 UK Biobank participants.

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.

LAVASET: Latent Variable Stochastic Ensemble of Trees. A novel ensemble method for correlated datasets.

LAVASET improves feature importance estimation in correlated datasets by incorporating correlation factors, achieving non-inferior prediction accuracy compared to Random Forests.

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.

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.

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.

Genome wide association analysis in dilated cardiomyopathy reveals two new key players in systolic heart failure on chromosome 3p25.1 and 22q11.23

This study performs a large GWAS on dilated cardiomyopathy, identifying two new loci and confirming two existing ones, with potential therapeutic implications.

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.

Genomic analysis reveals a functional role for myocardial trabeculae in adults

The paper identifies genetic associations with myocardial trabecular complexity using UK Biobank data and shows a causal link to ventricular function and electrical activity.

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.