John Barnard

TorchGWAS2 improves genome-wide association testing in related samples by using a deterministic variance-correction algorithm, achieving faster and more powerful results across large-scale omics data.

This paper performs a local ancestry-aware GWAS on SCD cohorts to identify novel genetic loci associated with eGFR, uncovering regions linked to inflammation, ECM integrity, and other pathways relevant to SCD nephropathy.

The paper identifies metabolic modules in PAH patients linked to RV-PV function using WGCNA and validates findings in independent cohorts.

The paper uses forward and reverse degradomics to analyze proteolytic landscapes in aortic aneurysms, identifying key proteases like MMP9 and CMA1 and their roles in extracellular matrix remodeling.

This study investigates the association between mosaic loss of Y chromosome (mLOY) and lung function, emphysema, and epigenetic aging in men across multiple cohorts.

cellSTAAR integrates single-cell ATAC-seq with whole-genome sequencing to enhance power and interpretation of rare variant association tests in non-coding regions.

The paper analyzes over 800,000 human genomes to assess penetrance of clinically relevant variants, finding that 95% of pLoF variants in severe diseases have explanations for lack of disease manifestation.

The paper analyzes circulating metabolites using genome-wide association data from the TOPMed program, identifying 1,778 loci and highlighting sex-specific genetic contributions.

The paper introduces MultiSTAAR, a statistical framework for multi-trait rare variant analysis in WGS studies, identifying new lipid trait associations in diverse populations.

Rare-variant depletion in 1kb windows of 76,156 gnomAD genomes, versus feature-adjusted mutation expectations, marks regulatory elements and outperforms seven alternative scores at flagging functional non-coding variants.

The paper develops a method to infer compound heterozygosity from exome sequencing data, achieving high accuracy in phasing rare variants for recessive disease diagnosis.

The paper identifies rs17171731 as the causal SNP regulating FAM13B expression linked to atrial fibrillation and shows its effect on cardiomyocyte gene expression and sodium current.

The paper introduces a framework for detecting noncoding rare variant associations using whole-genome sequencing data, applying it to lipid traits in the TOPMed program.

The paper estimates heritability for height and BMI using whole-genome sequence data and finds that rare variants contribute significantly to the missing heritability.

This study uses network-based methods to identify and validate metformin as a potential treatment for atrial fibrillation using human-derived atrial-like cardiomyocytes.

The paper reports whole-genome association analyses of sleep-disordered breathing traits in the NHLBI TOPMed program, identifying rare and common variant associations.

The paper identifies a SNP in the 3' UTR of the Pycard gene in mice that affects mRNA stability and inflammasome activity through CRISPR/Cas9 editing.

The paper uses whole genome sequencing to identify genetic loci associated with platelet aggregation, including novel variants in RGS18, SVEP1, and PEAR1.

This paper introduces RUTH, a new HWE test that accounts for population structure and genotype uncertainty, showing it reduces false positives compared to traditional methods.

Over 400 million variants, 97% below 1% frequency, emerge from deep whole-genome sequencing of 53,831 diverse TOPMed participants; TOPMed haplotypes enable imputation down to ~0.01% frequency.

The paper evaluates potential drug targets using loss-of-function genetic variants from gnomAD, highlighting the importance of deep curation and targeted recall studies for drug discovery.

From 125,748 exomes and 15,708 genomes, 443,769 high-confidence predicted loss-of-function variants yield LOEUF, a continuous gene intolerance score tracking mouse lethality, cell essentiality, and disease associations.

The paper develops an expression-based annotation metric to improve rare variant interpretation by filtering false-positive loss-of-function variants and identifying pathogenic variants in highly expressed exons.

Short-read genome sequencing of 14,891 diverse genomes yields 433,371 structural variants (SVs) for gnomAD; loss-constrained genes also resist duplication, and clinical SV carrier rates are benchmarked.

The paper analyzes loss-of-function variants in LRRK2 across large genomic datasets to assess the safety of partial LRRK2 inhibition as a Parkinson's disease therapy.

The paper systematically studies uORF variants in 15,708 genomes, showing they are under strong negative selection and contribute to disease.

The paper analyzes multi-nucleotide variants (MNVs) in 125,748 exomes and 15,708 genomes, identifying their distribution, mutational origins, and functional implications.

The paper analyzes de novo mutations in 1,465 genomes to show similar mutation rates across ancestries but reduced rates in the Amish population, with environmental factors possibly influencing mutation rates.

This study identifies AF-associated SNPs in SYNE2 that reduce SYNE21 expression and increase nuclear stiffness, potentially contributing to AF pathogenesis.

The paper assesses if genetic risk for atrial fibrillation explains cardioembolic stroke risk using genome-wide data from the Stroke Genetics Network.