Gil Atzmon

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.

This study develops a polygenic score to predict exceptional longevity by modeling pleiotropic genetic variants linked to aging-related traits, showing improved lifespan prediction and identifying potential drug targets.

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 miR-142-3p as a regulator of human longevity by modulating the insulin/IGF-1 signaling pathway in B-cells and mice.

The paper identifies a longevity-associated SMAD3 non-coding variant that impairs a cell-type specific enhancer, reducing inflammation and senescence in endothelial cells and improving healthspan in a mouse model.

The paper analyzes genome-wide data from medieval German Jews to show the Ashkenazi founder event occurred before the 14th century, with genetic heterogeneity not present in modern Ashkenazi Jews.

The paper identifies a SIRT6 variant enriched in centenarians that improves genome stability through enhanced mADPr activity and interaction with Lamin A.

The paper identifies ten new genes with coding variants linked to Crohn's disease risk using sequencing data from over 30,000 patients and 80,000 controls.

This study identifies 35 genes associated with circulating lipid levels using rare coding variants from 170,000 exomes across multiple ancestries.

The paper evaluates penetrance and variable expressivity of monogenic metabolic conditions using exome data from 77,184 individuals, finding that monogenic variants have larger effect sizes than polygenic scores but low penetrance.

The paper identifies ultra-rare exonic variants in an Ashkenazi Jewish founder population, implicating cadherins in schizophrenia through recurrent mutations and altered purifying selection.

This study identifies 100 loci associated with mitochondrial DNA copy number and finds causal links between mitochondrial function and mortality.

The paper examines how polygenic risk scores for Alzheimer's disease affect younger APOE4 carriers, finding earlier disease onset associated with higher PRS.

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.

This paper evaluates the potential benefits of using polygenic scores to select embryos for traits like height and cognitive function, finding limited gains with current predictors.

This study identifies rare genetic variants associated with type 2 diabetes using exome sequencing of 20,791 cases and 24,440 controls, and provides a Bayesian framework to improve variant prioritization.

This paper clusters T2D genetic loci using multi-trait associations to identify disease mechanisms and subtypes, finding distinct clinical outcomes linked to each cluster.

The paper sequenced a population-specific reference panel at high depth to improve imputation accuracy and variant filtering in the Ashkenazi Jewish population.