Lori L. Bonnycastle

This paper describes a scalable method to differentiate human pluripotent stem cells into hypothalamic arcuate neurons, which can model metabolic and reproductive disorders.

The paper identifies genetic factors influencing iPSC growth rates, finding rare variants in WDR54 and a polygenic background explaining most variance.

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 examines how physical activity and insulin resistance relate to skeletal muscle cell type abundance and gene expression in humans, finding inverse associations with specific cell types and gene expression patterns.

The paper uses direct RNA nanopore sequencing to identify RNA modification changes in human pancreatic beta-cells after glucose stimulation, finding 1,697 differentially modified sites linked to type 2 diabetes genes.

This study uses single-cell RNA sequencing to analyze gene expression changes in human pancreatic islets under different glucose conditions over 24 hours, identifying genes and modules associated with time, glucose exposure, and their interaction.

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 additional eQTL signals in adipose tissue and shows they contribute to cardiometabolic traits through gene dosage effects.

This study functionally interrogates 20 T2D-associated genes using isogenic hESC-derived β-like cells, identifying variants and genes linked to insulin production and lipotoxicity sensitivity.

This paper identifies miRNAs associated with type 2 diabetes and glycemic traits through genetic analysis of miRNA expression in human pancreatic islets.

The paper examines the association between adipose tissue ACE2 expression and cardio-metabolic risk factors, finding lower ACE2 levels linked to T2D, obesity, and inflammation-related cell type changes.

This study identifies 303 novel genetic signals associated with plasma metabolites in Finnish men, revealing biological insights into disease mechanisms.

This study identifies 12,111 SNPs associated with height from 5.4 million individuals, explaining most common SNP-based heritability and showing ancestry-specific prediction accuracy.

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 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 identifies genetic variants and transcripts associated with glycemic traits by analyzing exome-array data from 144,600 individuals, highlighting tissue-specific roles in glucose regulation.

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.