Francesco Mazzarotto

The complementary roles of rare variant burden scores and common variant polygenic risk scores in genetic risk prediction of complex disorders

This study combines rare variant burden scores and common variant polygenic risk scores to improve genetic risk prediction for schizophrenia, hypertrophic cardiomyopathy, and major depressive disorder.

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.

An Evidence-based Assessment of Genes in Dilated Cardiomyopathy

The paper curates and classifies genetic evidence for dilated cardiomyopathy (DCM), identifying 19 genes with strong or moderate evidence and highlighting gaps in understanding.

Computational prediction of protein subdomain stability in MYBPC3 enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation.

The paper uses STRUM to predict subdomain stability in MYBPC3 variants, showing that variants causing misfolding are associated with higher adverse event rates in HCM patients.

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.

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.

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%.

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.