Bruce M. Cohen

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 identifies a mitochondrial localization phenotype in psychosis patients and uses a cell-based assay to screen for compounds and genes affecting this phenotype.

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 investigates how the 22q11.2 deletion affects gene expression in neural progenitor cells and neurons, linking it to schizophrenia risk through altered presynaptic gene products.

The paper investigates SOX10 expression levels in schizophrenia and finds reduced SOX10 correlates with oligodendrocyte dysfunction and impaired white matter.

Exomes of 24,248 schizophrenia cases and 97,322 controls implicate ultra-rare damaging variants in 10 genes, including GRIN2A and GRIA3, with odds ratios of 3 to 50.

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

This study identifies Gαq as a mediator of clozapine effects in C. elegans by showing that mutations in dopamine receptors and Gq proteins alter clozapine susceptibility and developmental outcomes.