Daniel I. Chasman

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

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 uses pathway-specific polygenic scores to identify gene-adiposity interactions affecting liver biomarkers, finding more specific and interpretable results compared to standard polygenic scores and GWIS.

The paper introduces a decomposition approach to detect genetic modifiers of the relationship between dietary omega-3 fatty acids, plasma biomarkers, and hsCRP in the UK Biobank, improving statistical power.

The paper refines a gene-physical activity interaction affecting HDL-cholesterol by analyzing lipoprotein subfractions and exploring sex differences across multiple cohorts.

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.

This study identifies genetic signals associated with age at menarche, highlights genes involved in pubertal development, and links reproductive timing to later life disease risk.

This paper conducts a multi-ancestry time-to-event GWAS to identify genetic variants associated with incident cardiovascular disease in people with type 2 diabetes, finding three novel loci and confirming known CAD variants.

This study identifies 31 plasma proteins and expands genetic loci associated with PCOS, highlighting metabolic and hormonal influences and polygenic risk effects on cardio-metabolic outcomes.

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.

This study identifies 43 genomic loci associated with reproductive success in 785,604 individuals, showing ongoing natural selection at the FADS locus.

This study uses whole-genome sequencing to analyze mosaic chromosomal alterations across diverse ancestries, finding higher rates in certain populations and associations with germline variants.

This study identifies 135 genomic loci associated with venous thromboembolism risk through cross-ancestry GWAS and provides insights into biological pathways and potential therapeutic targets.

The paper identifies variance-quantitative trait loci (vQTLs) and gene-environment interactions (GEIs) for cardiometabolic serum biomarkers using UK Biobank data.

This GWAS identifies 123 migraine risk loci, including subtype-specific variants and novel targets, supporting neurovascular mechanisms in migraine.

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

The paper identifies five novel gene-diet interaction effects on HbA1c using UK Biobank data, highlighting interactions with dietary patterns and traits.

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.

The paper investigates the association between VKORC1 genetic variation and dementia risk, finding a link with vascular dementia but not general or Alzheimer dementia, and no effect of warfarin use on risk.

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.

This study identifies new genetic loci associated with myocardial infarction and coronary heart disease using genome-wide association analyses across multiple cohorts.

This study identifies 48 genetic variants associated with handedness using a large GWAS, highlighting polygenic nature and genetic links to neuropsychiatric traits.

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.