Dawood Darbar

Local ancestry-aware genome-wide meta-analysis uncovers novel genetic loci for sickle cell disease nephropathy

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.

Mosaic Loss of Y chromosome associates with lung function, emphysema and epigenetic aging

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

A titin missense variant drives atrial electrical remodeling and is associated with atrial fibrillation

The paper identifies a titin missense variant linked to atrial fibrillation through altered ion channel function and calcium homeostasis in human iPSC-derived atrial cardiomyocytes.

Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database

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.

A genome-wide mutational constraint map quantified from variation in 76,156 human genomes

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.

Inferring compound heterozygosity from large-scale exome sequencing data

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

Whole genome association testing in 333,100 individuals across three biobanks identifies rare non-coding single variant and genomic aggregate associations with height

Validation of human telomere length trans-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as novel human telomere length regulation genes

The paper validates novel telomere length regulation genes POP5 and KBTBD6 identified through trans-ancestry GWAS using functional experiments in blood cells.

Genetic control of mRNA splicing as a potential mechanism for incomplete penetrance of rare coding variants

This study shows that common splice-regulatory variants can reduce the pathogenicity of rare exonic variants by modulating mRNA splicing.

Myosin Light Chain Dephosphorylation by PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation

This study shows PPP1R12C overexpression in AF patients and mice leads to MLC2a dephosphorylation, reduced atrial contractility, and increased AF inducibility.

Clonal hematopoiesis is driven by aberrant activation of TCL1A

The paper develops PACER to infer clonal expansion rates from single timepoint data and identifies TCL1A activation as a mediator of clonal hematopoiesis fitness.

Genetic analyses of the QT interval and its components in over 250K individuals identifies new loci and pathways affecting ventricular depolarization and repolarization

Genomic and phenomic landscape of clonal hematopoiesis in over a million ancestrally diverse participants

This study analyzes clonal hematopoiesis in over a million diverse individuals, identifying 72 genome-wide significant loci and linking CHIP to various phenotypes.

Bidirectional Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of intermediate potential

The paper uses bidirectional Mendelian randomization to show LTL lengthening increases CHIP risk, while CHIP accelerates LTL shortening, with modest mediation between CHIP and CAD via LTL.

Whole-Genome Association Analyses of Sleep-disordered Breathing Phenotypes in the NHLBI TOPMed Program

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

Genome Sequencing Unveils a New Regulatory Landscape of Platelet Reactivity

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

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

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.

Novel genetic determinants of telomere length from a trans-ethnic analysis of 109,122 whole genome sequences in TOPMed

This study identifies 59 sentinel variants and two novel genes associated with telomere length using whole genome sequences from 109,122 trans-ethnic individuals.

Rare Non-coding Variation Identified by Large Scale Whole Genome Sequencing Reveals Unexplained Heritability of Type 2 Diabetes: Trans-Omics for Precision Medicine (TOPMed) Program

The paper identifies rare non-coding variants from whole genome sequencing in the TOPMed program, showing they contribute significantly to type 2 diabetes heritability.

Evaluating potential drug targets through human loss-of-function genetic variation

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.

The mutational constraint spectrum quantified from variation in 141,456 humans

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.

Transcript expression-aware annotation improves rare variant discovery and interpretation

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.

Human loss-of-function variants suggest that partial LRRK2 inhibition is a safe therapeutic strategy for Parkinsons disease

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.

Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals

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

Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes

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

Inherited Causes of Clonal Hematopoiesis of Indeterminate Potential in TOPMed Whole Genomes

The paper identifies germline genetic variants associated with clonal hematopoiesis of indeterminate potential (CHIP) using whole genome sequences from the TOPMed program.

GWAS of QRS Duration Identifies New Loci Specific to Hispanic/Latino Populations

This study conducts a GWAS on QRS duration in Hispanic/Latino populations, identifying two new loci and confirming most previously known SNPs.

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals

The paper analyzes whole genome sequences from 16,324 individuals to identify genetic variants associated with blood lipid levels and develops a polygenic score for LDL-C.

Mutations in RPL3L and MYZAP increase risk of atrial fibrillation

This study identifies mutations in RPL3L and MYZAP as risk factors for atrial fibrillation through genome-wide association analysis and functional validation.