Hugh C Watkins

Genotype-Phenotype Correlations Identify Phenotypic Differences in Sarcomere Mutation-Positive Hypertrophic Cardiomyopathy in the NHLBI HCM Registry

The paper identifies phenotypic differences in sarcomere mutation-positive hypertrophic cardiomyopathy using CMR data from the NHLBI HCM Registry, resolving prior discrepancies through meta-analysis.

Unmasking Supervillin: SVIL haploinsufficiency causes hypertrophic cardiomyopathy by impairing mechanotransduction and cellular energetics.

This study identifies SVIL haploinsufficiency as a cause of hypertrophic cardiomyopathy by impairing mechanotransduction and cellular energetics, with potential therapeutic implications for mitochondrial-targeted treatments.

An ALPK3 truncation variant causing autosomal dominant hypertrophic cardiomyopathy is partially rescued by mavacamten

This study identifies an ALPK3 truncation variant causing HCM and shows that mavacamten partially rescues cardiac contractility and calcium handling defects in a mouse model.

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.

Whole genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver roles.

This study uses whole genome sequencing to identify 18 novel genetic loci associated with plasma fibrinogen levels, including variants more common in African populations and linked to liver-related traits and disease.

An autosomal dominant cardiac arrhythmia syndrome, ST Depression Syndrome, is caused by the de novo creation of a cardiomyocyte enhancer.

The paper identifies a de novo enhancer mutation in KCNB1 causing ST Depression Syndrome, a cardiac arrhythmia, and shows it can be predicted by a deep neural network.

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.

Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants.

A coronary artery disease GWAS of 181,522 cases among 1,165,690 participants yields 241 associations (54 new); an eight-predictor consensus nominates 185 candidate causal genes, 94 with ≥3 predictors.

Random glucose GWAS in 493,036 individuals provides insights into diabetes pathophysiology, complications and treatment stratification

This study performs a GWAS on random glucose measurements in 493,036 individuals, identifying 128 loci associated with glycaemic traits and providing insights into diabetes biology and treatment.

Bi-allelic MCM10 mutations cause telomere shortening with immune dysfunction and cardiomyopathy

This study identifies bi-allelic MCM10 mutations causing telomere shortening, immune dysfunction, and cardiomyopathy by impairing DNA replication and telomerase activity.

Heritability and family-based GWAS analyses of the N-acyl ethanolamine and ceramide plasma lipidome

The paper assesses heritability and identifies genetic variants influencing plasma NAE and CER lipid levels using GWAS in a family cohort.

Heterozygous ATP-binding Cassette Transporter G5 Gene Deficiency and Risk of Coronary Artery Disease

This study investigates the impact of heterozygous ABCG5 LoF variants on LDL-C levels and CAD risk, finding a significant association with elevated LDL-C and doubled CAD risk.

Data-driven modelling of mutational hotspots and in-silico predictors in hypertrophic cardiomyopathy

The paper introduces methods to improve disease-gene association and variant pathogenicity interpretation by incorporating missense residue position information.

Whole-genome sequencing of rare disease patients in a national healthcare system

This study uses whole-genome sequencing in a national healthcare system to diagnose rare diseases and discover new aetiological variants, identifying 95 Mendelian associations and 4 novel non-coding disease-causing variants.

A missense variant in Mitochondrial Amidoxime Reducing Component 1 gene and protection against liver disease

The paper identifies a missense variant in the MARC1 gene associated with protection against cirrhosis and lower liver enzyme and cholesterol levels.

Metabolic Profiling of Aortic Stenosis and Hypertrophic Cardiomyopathy Identifies Mechanistic Contrasts in Substrate Utilisation

This study compares metabolic profiles in aortic stenosis and hypertrophic cardiomyopathy, identifying distinct substrate utilization patterns and PPAR- signaling differences.

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%.

MYBPC3 Mutations cause Hypertrophic Cardiomyopathy by Dysregulating Myosin: Implications for Therapy

The paper shows that MYBPC3 mutations disrupt myosin relaxation states, leading to hyper-contractility in HCM, and that targeting myosin can alleviate these effects.

Genomic risk prediction of coronary artery disease in nearly 500,000 adults: implications for early screening and primary prevention

This paper develops a genomic risk score for coronary artery disease using 1.7 million variants and tests it in UK Biobank, showing it outperforms conventional risk factors in predicting CAD risk.

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples

The paper reassesses the pathogenicity of Mendelian genes by comparing rare variation frequencies between cardiomyopathy cases and large reference datasets, identifying false positives and overly conservative variant assessments.